Impact of MtrA on phosphate metabolism genes and the response to altered phosphate conditions in Streptomyces

Phosphate metabolism is known to be regulated by the PhoPR regulatory system in Streptomyces and some other bacteria. In this study, we report that MtrA also regulates phosphate metabolism in Streptomyces. Our data showed that, in Streptomyces coelicolor, MtrA regulates not only phosphate metabolism genes such as phoA but also phoP under different phosphate conditions, including growth on rich complex media without added inorganic phosphate and on defined media with low or high concentrations of inorganic phosphate. Cross-regulation was also observed among mtrA, phoP and glnR under these conditions. We demonstrated both in vitro and in vivo binding of MtrA to the promoter regions of genes associated with phosphate metabolism and to the intergenic region between phoR and phoU, indicating that these phosphate metabolism genes are targets of MtrA. We further showed that MtrA in S. lividans and S. venezuelae has detectable regulatory effects on expression of phosphate metabolism genes. Additionally, the MtrA homologue from Corynebacterium glutamicum bound predicted MtrA sites of multiple phosphate metabolism genes, implying its potential for regulating phosphate metabolism in this species. Overall, our findings support MtrA as a major regulator for phosphate metabolism in Streptomyces and also potentially in other actinobacteria.     

Differential induction of polar and non‐polar metabolism during wound‐induced suberization in potato (Solanum tuberosum L.) tubers

Wound‐induced suberin deposition involves the temporal and spatial coordination of phenolic and fatty acid metabolism. Phenolic metabolism leads to both soluble metabolites that accumulate as defense compounds as well as hydroxycinnamoyl derivatives that form the basis of the poly(phenolic) domain found in suberized tissue. Fatty acid metabolism involves the biosynthesis of very‐long‐chain fatty acids, 1‐alkanols, ω‐hydroxy fatty acids and α,ω‐dioic acids that form a poly(aliphatic) domain, commonly referred to as suberin. Using the abscisic acid (ABA) biosynthesis inhibitor fluridone (FD), we reduced wound‐induced de novo biosynthesis of ABA in potato tubers, and measured the impact on the expression of genes involved in phenolic metabolism (StPAL1, StC4H, StCCR, StTHT), aliphatic metabolism (StCYP86A33, StCYP86B12, StFAR3, StKCS6), metabolism linking phenolics and aliphatics (StFHT) or acyl chains and glycerol (StGPAT5, StGPAT6), and in the delivery of aliphatic monomers to the site of suberization (StABCG1). In FD‐treated tissue, both aliphatic gene expression and accumulation of aliphatic suberin monomers were delayed. Exogenous ABA restored normal aliphatic suberin deposition in FD‐treated tissue, and enhanced aliphatic gene expression and poly(aliphatic) domain deposition when applied alone. By contrast, phenolic metabolism genes were not affected by FD treatment, while FD + ABA and ABA treatments slightly enhanced the accumulation of polar metabolites. These data support a role for ABA in the differential induction of phenolic and aliphatic metabolism during wound‐induced suberization in potato.     

Uniqueness of Entamoeba sulfur metabolism: sulfolipid metabolism that plays pleiotropic roles in the parasitic life cycle

Sulfur metabolism is ubiquitous and terminally synthesizes various biomolecules that are crucial for organisms, such as sulfur‐containing amino acids and co‐factors, sulfolipids and sulfated saccharides. Entamoeba histolytica, a protozoan parasite responsible for amoebiasis, possesses the unique sulfur metabolism features of atypical localization and its terminal product being limited to sulfolipids. Here, we present an overall scheme of E. histolytica sulfur metabolism by relating all sulfotransferases and sulfatases to their substrates and products. Furthermore, a novel sulfur metabolite, fatty alcohol disulfates, was identified and shown to play an important role in trophozoite proliferation. Cholesteryl sulfate, another synthesized sulfolipid, was previously demonstrated to play an important role in encystation, a differentiation process from proliferative trophozoite to dormant cyst. Entamoeba survives by alternating between these two distinct forms; therefore, Entamoeba sulfur metabolism contributes to the parasitic life cycle via its terminal products. Interestingly, this unique feature of sulfur metabolism is not conserved in the nonparasitic close relative of Entamoeba, Mastigamoeba, because lateral gene transfer‐mediated acquisition of sulfatases and sulfotransferases, critical enzymes conferring this feature, has only occurred in the Entamoeba lineage. Hence, our findings suggest that sulfolipid metabolism has a causal relationship with parasitism.     

Effect of glyphosate on indole-3-acetic acid metabolism in tolerant and susceptible plants

A comparison study was conducted on the effect of glyphosate (N-[phosphonomethyl]glycine) on indole-3-[2-¹⁴C]acetic acid (IAA) metabolism, ethylene production, and growth of 7-day-old seedlings of different plants. The plants tested were American germander (Teucrium canadense L.), soybean (Glycine max L. Merr.), pea (Pisum sativum L. cv. Alaska and Little marvel), mungbean (Vigna radiata L.), and buckwheat (Fagopyrum esculentum Moench). A spray with 2 mM glyphosate affected IAA metabolism to a varied degree. The induced increase of IAA metabolism was greater in buckwheat, Alaska pea, and mungbean than soybean, Little marvel pea, and American germander. The increased IAA metabolism was correlated with the inhibition of growth and with the decrease of ethylene production.The natural rate of IAA metabolism was markedly different among the plant species and cultivars tested and appeared to be related to the sensitivity of the plants to glyphosate. American germander and Little marvel pea with high rates of IAA metabolism were more tolerant to glyphosate than buckwheat and Alaska pea, which had low rates of IAA metabolism. Plants with a high natural rate of IAA metabolism were probably less dependent on IAA and thus less susceptible to glyphosate.     

iTRAQ analysis reveals the effect of gabD and sucA gene knockouts on lysine metabolism and crystal protein formation in Bacillus thuringiensis

Lysine metabolism plays an important role in the formation of the insecticidal crystal proteins of Bacillus thuringiensis (Bt). The genes lam, gabD and sucA encode three key enzymes of the lysine metabolic pathway in Bt4.0718. The lam gene mainly affects the cell growth at stable period, negligibly affected sporulation and insecticidal crystal protein (ICP) production. While, the deletion mutant strains of the gabD and sucA genes showed that the growth, sporulation and crystal protein formation were inhibited, cells became slender, and insecticidal activity was significantly reduced. iTRAQ proteomics and qRT-PCR used to analyse the differentially expressed protein (DEP) between the two mutant strains and the wild type strain. The functions of DEPs were visualized and statistically classified, which affect bacterial growth and metabolism by regulating biological metabolism pathways: the major carbon metabolism pathways, amino acid metabolism, oxidative phosphorylation pathways, nucleic acid metabolism, fatty acid synthesis and peptidoglycan synthesis. The gabD and sucA genes in lysine metabolic pathway are closely related to the sporulation and crystal proteins formation. The effects of DEPs and functional genes on basic cellular metabolic pathways were studied to provide new strategies for the construction of highly virulent insecticidal strains, the targeted transformation of functional genes.     

Altered metabolism in cancer

Cancer cells have different metabolic requirements from their normal counterparts. Understanding the consequences of this differential metabolism requires a detailed understanding of glucose metabolism and its relation to energy production in cancer cells. A recent study in BMC Systems Biology by Vasquez et al. developed a mathematical model to assess some features of this altered metabolism. Here, we take a broader look at the regulation of energy metabolism in cancer cells, considering their anabolic as well as catabolic needs.     

Effects of Acetyl-l-Carnitine and Myo-Inositol on High-Energy Phosphate and Membrane Phospholipid Metabolism in Zebra Fish: A 31P-NMR-Spectroscopy Study

Acetyl-l-carnitine (ALCAR) and myo-inositol are reported to enhance motor activity in animal models; modulate membrane phospholipid metabolism (ALCAR and myo-inositol) and high-energy phosphate metabolism (ALCAR) back to normal; and be effective treatments of major depression in humans. Fish in general and zebra fish in particular present unique animal models for the in vivo study of high-energy phosphate and membrane phospholipid metabolism by noninvasive in vivo ^31P NMR. This ^31P NMR study of free-swimming zebra fish showed that both ALCAR and myo-inositol decreased levels of phosphodiesters and inorganic orthophosphate and increased levels of PCr in the fish. These findings demonstrate both ALCAR and myo-inositol modulate membrane phospholipid and high-energy phosphate metabolism in free-swimming zebra fish.     

Reconstitution of oxaloacetate metabolism in the tricarboxylic acid cycle in Synechocystis sp. PCC 6803: discovery of important factors that directly affect the conversion of oxaloacetate

The tricarboxylic acid (TCA) cycle is one of the most important metabolic pathways in nature. Oxygenic photoautotrophic bacteria, cyanobacteria, have an unusual TCA cycle. The TCA cycle in cyanobacteria contains two unique enzymes that are not part of the TCA cycle in other organisms. In recent years, sustainable metabolite production from carbon dioxide using cyanobacteria has been looked at as a means to reduce the environmental burden of this gas. Among cyanobacteria, the unicellular cyanobacterium Synechocystis sp. PCC 6803 (Synechocystis 6803) is an optimal host for sustainable metabolite production. Recently, metabolite production using the TCA cycle in Synechocystis 6803 has been carried out. Previous studies revealed that the branch point of the oxidative and reductive TCA cycles, oxaloacetate metabolism, plays a key role in metabolite production. However, the biochemical mechanisms regulating oxaloacetate metabolism in Synechocystis 6803 are poorly understood. Concentrations of oxaloacetate in Synechocystis 6803 are extremely low, such that in vivo analysis of oxaloacetate metabolism does not seem realistic. Therefore, using purified enzymes, we reconstituted oxaloacetate metabolism in Synechocystis 6803 in vitro to reveal the regulatory mechanisms involved. Reconstitution of oxaloacetate metabolism revealed that pH, Mg²⁺ and phosphoenolpyruvate are important factors affecting the conversion of oxaloacetate in the TCA cycle. Biochemical analyses of the enzymes involved in oxaloacetate metabolism in this and previous studies revealed the biochemical mechanisms underlying the effects of these factors on oxaloacetate conversion. In addition, we clarified the function of two l- malate dehydrogenase isozymes in oxaloacetate metabolism. These findings serve as a basis for various applications of the cyanobacterial TCA cycle.     

Trichome regulator SlMIXTA‐like directly manipulates primary metabolism in tomato fruit

Trichomes are storage compartments for specialized metabolites in many plant species. In trichome, plant primary metabolism is significantly changed, providing substrates for downstream secondary metabolism. However, little is known of how plants coordinate trichome formation and primary metabolism regulation. In this report, tomato (Solanum lycopersicum) trichome regulator SlMIXTA‐like is indicated as a metabolic regulation gene by mGWAS analysis. Overexpression of SlMIXTA‐like in tomato fruit enhances trichome formation. In addition, SlMIXTA‐like can directly bind to the promoter region of gene encoding 3‐deoxy‐7‐phosphoheptulonate synthase (SlDAHPS) to activate its expression. Induction of SlDAHPS expression enhances shikimate pathway activities and provides substrates for downstream secondary metabolism. Our data provide direct evidence that trichome regulator can directly manipulate primary metabolism, in which way plants can coordinate metabolic regulation and the formation of storage compartments for specialized metabolites. The newly identified SlMIXTA‐like can be used for future metabolic engineering.     

Production of selenium nanoparticles occurs through an interconnected pathway of sulphur metabolism and oxidative stress response in Pseudomonas putida KT2440

The soil bacterium Pseudomonas putida KT2440 has been shown to produce selenium nanoparticles aerobically from selenite; however, the molecular actors involved in this process are unknown. Here, through a combination of genetic and analytical techniques, we report the first insights into selenite metabolism in this bacterium. Our results suggest that the reduction of selenite occurs through an interconnected metabolic network involving central metabolic reactions, sulphur metabolism, and the response to oxidative stress. Genes such as sucA, D2HGDH and PP_3148 revealed that the 2-ketoglutarate and glutamate metabolism is important to convert selenite into selenium. On the other hand, mutations affecting the activity of the sulphite reductase decreased the bacteria's ability to transform selenite. Other genes related to sulphur metabolism (ssuEF, sfnCE, sqrR, sqr and pdo2) and stress response (gqr, lsfA, ahpCF and sadI) were also identified as involved in selenite transformation. Interestingly, suppression of genes sqrR, sqr and pdo2 resulted in the production of selenium nanoparticles at a higher rate than the wild-type strain, which is of biotechnological interest. The data provided in this study brings us closer to understanding the metabolism of selenium in bacteria and offers new targets for the development of biotechnological tools for the production of selenium nanoparticles.     

Influence du lindane sur le métabolisme respiratoire d'Asellus aquaticus L. Relation concentration — perturbation

The respiratory metabolism of Asellus aquaticus L. was investigated after short-term exposure to lindane poisoning at 15 °C. After 48 h, oxygen consumption was individually recorded with a polarographic method using a Clark electrode and a Copenhagen radiometer.The average oxygen consumption by poisoned individuals is higher than controls at concentrations lower than 8 µg·1^–1 but decreases to become lower than controls at higher dosages. If the metabolism of individuals is expressed as a function of weight, we find no significant correlation between weight and metabolism of poisoned Asellus, as opposed to controls. This result can be explained by the fact that poisoning intensity decreases with body weight at a given insecticide concentration, whereas metabolism increases as a function of weight. As a consequence there is apparently a lack of correlation between weight and metabolism amongst poisoned Asellus at dosages higher than 2 µg·1^–1. However, if metabolism is expressed as a metabolic ratio, a good correlation is observed between metabolism and weight of poisoned Asellus, the metabolic perturbation being significant at 4 µg·1^–1 and higher concentrations.These results prompt us to conclude that, during the initial step of intoxication, an increase of the oxygen consumption occurs under weak poisoning conditions, while higher concentrations of insecticide give rise to a decrease in metabolism.

     

RNase1 can modulate gut microbiota and metabolome after Aeromonas hydrophila infection in blunt snout bream

Pancreatic ribonuclease (RNase1) of Megalobrama amblycephala exhibits both antimicrobial and digestive activity. The gut microbiome improve the digestion and metabolic capacity and enhance the functioning of the immune system of the host against pathogenic bacteria. In this study, we aimed to assess the protective effect of RNase1 on Aeromonas hydrophila-induced inflammation and intestinal microbial metabolism. Megalobrama amblycephala were randomly divided into three groups: control (injected PBS), infection (A. hydrophila-injected), and treatment group (RNase1 pretreatment 24 h before the A. hydrophila injection). The morphological symptoms were significantly alleviated by RNase1. RNase1 reshaped the perturbed gut microbiota by upregulating Proteobacteria and Vibrio richness and downregulating Firmicutes, Chlamydiae, Bacillus, and Gemmobacter richness. The lysophosphatidylcholine, (±) 17 HETE, D- (+) -cellobiose, and PC (20:5) in the treatment group were restored by RNase 1 protein treatment to the level of the control group. In the treatment group, phospholipid metabolism, fatty acid metabolism, glucose metabolism and lipid metabolism were different from the control and infection groups. The proinflammatory factors concentration in intestinal samples significantly increased after A. hydrophila infection. Our results revealed that RNase1 plays an important role in resistance to pathogen invasion, reducing inflammation, and improving intestinal function, thus inhibiting the occurrence of disease.     

Glycogen debranching enzyme 6 (AGL), enolase 1 (ENOSF1), ectonucleotide pyrophosphatase 2 (ENPP2_1), glutathione S-transferase 3 (GSTM3_3) and mannosidase (MAN2B2) metabolism computational network analysis between chimpanzee and human left cerebrum

We identified significantly higher expression of the genes glycogen debranching enzyme 6 (AGL), enolase 1 (ENOSF1), ectonucleotide pyrophosphatase 2 (ENPP2_1), glutathione S-transferase 3 (GSTM3_3) and mannosidase (MAN2B2) from human left cerebrums versus chimpanzees. Yet the distinct low- and high-expression AGL, ENOSF1, ENPP2_1, GSTM3_3 and MAN2B2 metabolism networks between chimpanzee and human left cerebrum remain to be elucidated. Here, we constructed low- and high-expression activated and inhibited upstream and downstream AGL, ENOSF1, ENPP2_1, GSTM3_3 and MAN2B2 metabolism network between chimpanzee and human left cerebrum in GEO data set by gene regulatory network inference method based on linear programming and decomposition procedure, under covering AGL, ENOSF1, ENPP2_1, GSTM3_3 and MAN2B2 pathway and matching metabolism enrichment analysis by CapitalBio MAS 3.0 integration of public databases, including Gene Ontology, KEGG, BioCarta, GenMapp, Intact, UniGene, OMIM, etc. Our results show that the AGL, ENOSF1, ENPP2_1, GSTM3_3 and MAN2B2 metabolism network has more activated and less inhibited molecules in chimpanzee, but less activated and more inhibited in the human left cerebrum. We inferred stronger carbohydrate, glutathione and proteoglycan metabolism, ATPase activity, but weaker base excision repair, arachidonic acid and drug metabolism as a result of inducing cell growth in low-expression AGL, ENOSF1, ENPP2_1, GSTM3_3 and MAN2B2 metabolism network of chimpanzee left cerebrum; whereas stronger lipid metabolism, amino acid catabolism, DNA repair but weaker inflammatory response, cell proliferation, glutathione and carbohydrate metabolism as a result of inducing cell differentiation in high-expression AGL, ENOSF1, ENPP2_1, GSTM3_3 and MAN2B2 metabolism network of human left cerebrum. Our inferences are consistent with recent reports and computational activation and inhibition gene number patterns, respectively.     

Expression of a Brassica Isopropylmalate Synthase Gene in Arabidopsis Perturbs Both Glucosinolate and Amino Acid Metabolism

Isopropylmalate synthase (IPMS) is a key enzyme in the biosynthesis of the essential amino acid leucine, and thus primary metabolism. In Arabidopsis, the functionally similar enzyme, methythiolalkylmalate synthase (MAM), is an important enzyme in the elongation of methionine prior to glucosinolate (GSL) biosynthesis, as part of secondary metabolism. We describe the cloning of an IPMS gene from Brassica, BatIMS, and its functional characterisation by heterologous expression in E. coli and Arabidopsis. Over expression of BatIMS in Arabidopsis resulted in plants with an aberrant phenotype, reminiscent of mutants in GSL biosynthesis. Metabolite analyses showed that these plants had both perturbed amino acid metabolism and enhanced levels of GSLs. Microarray profiling showed that BatIMS over expression caused up regulation of the genes for methionine-derived GSL biosynthesis, and down regulation of genes involved in leucine catabolism, in addition to perturbed expression of genes involved in auxin and ethylene metabolism. The results illustrate the cross talk that can occur between primary and secondary metabolism within transgenic plants. Electronic Supplementary Material Supplementary material is available for this article at and is accessible for authorized users.     

腾格里沙漠东南缘藻结皮与藓结皮放线菌多样性及其潜在代谢功能

放线菌作为干旱、半干旱环境中生物土壤结皮(Biological Soil Crusts,BSCs)组成的重要生命存在形式之一,不仅是潜在临床有用天然产物化学多样性的重要来源,也是该生态系统物质循环与能量流动的重要参与者。以腾格里沙漠东南缘广泛分布的藻结皮和藓结皮为研究对象,通过宏基因组测序比较分析两种BSCs放线菌种群的分布特征、组成及其潜在代谢功能。结果表明,腾格里沙漠东南缘藻结皮与藓结皮土壤微生物组主要形成以地嗜皮菌属、红色杆菌属、类诺卡氏菌属、游动放线菌属、芽生球菌属、链霉菌属、贫养杆菌属、糖丝菌属、土壤红杆菌属、假诺卡氏菌属、小单孢子菌属、康奈斯氏杆菌属、大理石雕菌属、小月菌属以及弗兰克氏菌属等为主要类群的放线菌群落结构,在两种BSCs类型之间各属分布存在差异。藓结皮中放线菌参与的氨基糖与核苷酸糖代谢、原核生物中的碳固定途径、丁酸代谢、丙酸代谢、丙氨酸/天门冬氨酸和谷氨酸代谢、甲烷代谢、2-羰基羧酸代谢、肽聚糖生物合成、淀粉与蔗糖代谢以及缬氨酸/亮氨酸与异亮氨酸降解显著高于藻结皮。藓结皮中地嗜皮菌属和红色杆菌属对相对丰度前10的代谢功能分类的贡献度显著低于藻结皮,而类诺卡氏菌属...     

Carbohydrate Metabolism of the Saccharolytic Alkaliphilic Anaerobes Halonatronum saccharophilum,Amphibacillus fermentum,and Amphibacillus tropicus

The saccharolytic anaerobic bacteria Halonatronum saccharophilum, Amphibacillus fermentum, and Amphibacillus tropicus produce formate, the main fermentation product. In the alkaliphilic community, formate is used as the preferential substrate for sulfate reduction. To reveal the pathways of carbohydrate fermentation by these bacteria, the activity of the key enzymes of carbohydrate metabolism and their pH dependence was studied. It was established that H. saccharophilum utilized glucose by the fructose bisphosphate and hexose monophosphate pathways, and A. tropicus, by the fructose bisphosphate and Entner–Doudoroff pathways. The activity of the key enzymes of all three pathways of glucose metabolism was detected in Amphibacillus fermentum. According to the data obtained, the glucose catabolism in H. saccharophilum, A. fermentum, and A. tropicus mainly proceeds via the fructose bisphosphate pathway. The pH optima of the key enzymes of the glucose metabolism of the alkaliphiles are shifted to alkaline values. In A. tropicus, formate is formed from pyruvate under the action of pyruvate formate-lyase; and in the haloanaerobe H. saccharophilum, formate dehydrogenase is involved in formate metabolism.     

Verticillium dahliae VdBre1 is required for cotton infection by modulating lipid metabolism and secondary metabolites

The soil-borne ascomycete Verticillium dahliae causes wilt disease in more than two hundred dicotyledonous plants including the economically important crop cotton, and results in a severe reduction in cotton fiber yield and quality. During infection, V. dahliae secretes numerous secondary metabolites, which act as toxic factors to promote the infection process. However, the mechanism underlying how V. dahliae secondary metabolites regulate cotton infection remains largely unexplored. In this study, we report that VdBre1, an ubiquitin ligase (E3) enzyme to modify H2B, regulates radial growth and conidia production of V. dahliae. The VdBre1 deletion strains show nonpathogenic symptoms on cotton, and microscopic inspection and penetration assay indicated that penetration ability of the ∆VdBre1 strain was dramatically reduced. RNA-seq revealed that a total of 1643 differentially expressed genes between the ∆VdBre1 strain and the wild type strain V592, among which genes related to lipid metabolism were significantly overrepresented. Remarkably, the volume of lipid droplets in the ∆VdBre1 conidia was shown to be smaller than that of wild-type strains. Further metabolomics analysis revealed that the pathways of lipid metabolism and secondary metabolites, such as steroid biosynthesis and metabolism of terpenoids and polyketides, have dramatically changed in the ∆VdBre1 metabolome. Taken together, these results indicate that VdBre1 plays crucial roles in cotton infection and pathogenecity, by globally regulating lipid metabolism and secondary metabolism of V. dahliae.     

Staphylococcus aureus ClpC ATPase is a late growth phase effector of metabolism and persistence

Staphylococcus aureus Clp ATPases (molecular chaperones) alter normal physiological functions including an aconitase‐mediated effect on post‐stationary growth, acetate catabolism, and entry into death phase (Chatterjee et al., J. Bacteriol. 2005, 187, 4488–4496). In the present study, the global function of ClpC in physiology, metabolism, and late‐stationary phase survival was examined using DNA microarrays and 2‐D PAGE followed by MALDI‐TOF MS. The results suggest that ClpC is involved in regulating the expression of genes and/or proteins of gluconeogenesis, the pentose‐phosphate pathway, pyruvate metabolism, the electron transport chain, nucleotide metabolism, oxidative stress, metal ion homeostasis, stringent response, and programmed cell death. Thus, one major function of ClpC is balancing late growth phase carbon metabolism. Furthermore, these changes in carbon metabolism result in alterations of the intracellular concentration of free NADH, the amount of cell‐associated iron, and fatty acid metabolism. This study provides strong evidence for ClpC as a critical factor in staphylococcal energy metabolism, stress regulation, and late‐stationary phase survival; therefore, these data provide important insight into the adaptation of S. aureus toward a persister state in chronic infections.     

Interrelationships between mitochondrial fusion, energy metabolism and oxidative stress during development in Caenorhabditis elegans

Mitochondria are known to be dynamic structures with the energetically and enzymatically mediated processes of fusion and fission responsible for maintaining a constant flux. Mitochondria also play a role of reactive oxygen species production as a byproduct of energy metabolism. In the current study, interrelationships between mitochondrial fusion, energy metabolism and oxidative stress on development were explored using a fzo-1 mutant defective in the fusion process and a mev-1 mutant overproducing superoxide from mitochondrial electron transport complex II of Caenorhabditis elegans. While growth and development of both single mutants was slightly delayed relative to the wild type, the fzo-1;mev-1 double mutant experienced considerable delay. Oxygen sensitivity during larval development, superoxide production and carbonyl protein accumulation of the fzo-1 mutant were similar to wild type. fzo-1 animals had significantly lower metabolism than did N2 and mev-1. These data indicate that mitochondrial fusion can profoundly affect energy metabolism and development.