The centrosome in vertebrates: more than a microtubule-organizing center

The somatic cells of all higher animals contain a single minute organelle called the centrosome. For years, the functions of the centrosome were thought to revolve around its ability to nucleate and organize the various microtubule arrays seen in interphase and mitosis. But the centrosome is more than just a microtubule-organizing center. Recent work reveals that this organelle is essential for cell-cycle progression and that this requirement is independent of its ability to organize microtubules. Here, we review the various functions attributed to the centrosome and ask which are essential for the survival and reproduction of the cell, the organism, or both.     

ER‐phagy: selective autophagy of the endoplasmic reticulum

Eukaryotic cells adequately control the mass and functions of organelles in various situations. Autophagy, an intracellular degradation system, largely contributes to this organelle control by degrading the excess or defective portions of organelles. The endoplasmic reticulum (ER) is an organelle with distinct structural domains associated with specific functions. The ER dynamically changes its mass, components, and shape in response to metabolic, developmental, or proteotoxic cues to maintain or regulate its functions. Therefore, elaborate mechanisms are required for proper degradation of the ER. Here, we review our current knowledge on diverse mechanisms underlying selective autophagy of the ER, which enable efficient degradation of specific ER subdomains according to different demands of cells.     

Mycoplasma pneumoniae J-domain protein required for terminal organelle function

The cell wall-less prokaryote Mycoplasma pneumoniae causes tracheobronchitis and primary atypical pneumonia in humans. Colonization of the respiratory epithelium requires proper assembly of a complex, multifunctional, polar terminal organelle. Loss of a predicted J-domain protein also having domains unique to mycoplasma terminal organelle proteins (TopJ) resulted in a non-motile, adherence-deficient phenotype. J-domain proteins typically stimulate ATPase activity of Hsp70 chaperones to bind nascent peptides for proper folding, translocation or macromolecular assembly, or to resolve stress-induced protein aggregates. By Western immunoblotting all defined terminal organelle proteins examined except protein P24 remained at wild-type levels in the topJ mutant; previous studies established that P24 is required for normal initiation of terminal organelle formation. Nevertheless, terminal organelle proteins P1, P30, HMW1 and P41 failed to localize to a cell pole, and when evaluated quantitatively, P30 and HMW1 foci were undetectable in >40% of cells. Complementation of the topJ mutant with the recombinant wild-type topJ allele largely restored terminal organelle development, gliding motility and cytadherence. We propose that this J-domain protein, which localizes to the base of the terminal organelle in wild-type M. pneumoniae , functions in the late stages of assembly, positioning, or both, of nascent terminal organelles.     

Mycoplasmas: a distinct cytoskeleton for wall-less bacteria

The bacterial genus Mycoplasma includes a large number of highly genomically-reduced species which in nature are associated with hosts either commensally or pathogenically. Several Mycoplasma species, including Mycoplasma pneumoniae, feature a multifunctional polar structure, the terminal organelle. Essential for colonization of the host and for gliding motility, the terminal organelle is associated with an internal cytoskeleton crucial to its assembly and function. This cytoskeleton is structurally and compositionally novel as compared with the cytoskeletons of other organisms, including other bacteria, is also involved in the cell division process. In this review we discuss the cytoskeletal structures and protein components of the attachment organelle and how they might interact and contribute to its various functions.     

Investigation of peroxisome biogenesis revealed possible new roles for autophagy components

Precursor aminopeptidase I oligomerizes in the cytosol and is imported into the vacuole as a dodecamer via the cytoplasm-to-vacuole targeting (Cvt) pathway or autophagy. However, this is not the only example for the import of oligomeric protein complexes into an organelle. During peroxisome biogenesis folded and oligomeric proteins can be imported into the lumen of the organelle. The mechanism of this transport is still unknown. In this article, we point out mechanistic parallels between peroxisome biogenesis and the Cvt pathway or autophagy. Furthermore, we summarize our recently published investigation on a possible overlap between these pathways. Our investigation revealed new insights into autophagy and the Cvt pathway and possible new functions of Cvt4p, Cvt8p and Atg14p in organelle biogenesis or stability.(1).     

Organelle acidification and disease

A subset of cellular compartments maintain acidic interior environments that are critical for the specific functions of each organelle and for cell growth and survival in general. The pH of each organelle reflects the balance between proton pumping, counterion conductance, and proton leak. Alterations in steady-state organelle pH due to defects in either proton pumping activity or counterion conductance have been suggested to contribute to the pathology of several diseases; however, definitive evidence remains elusive. This review describes recent evidence for the misregulation of organelle pH in the progression of cancer, Dent's disease, and cystic fibrosis .     

Electron cryotomography of Mycoplasma pneumoniae mutants correlates terminal organelle architectural features and function

The Mycoplasma pneumoniae terminal organelle functions in adherence and gliding motility and is comprised of at least eleven substructures. We used electron cryotomography to correlate impaired gliding and adherence function with changes in architecture in diverse terminal organelle mutants. All eleven substructures were accounted for in the prkC, prpC and P200 mutants, and variably so for the HMW3 mutant. Conversely, no terminal organelle substructures were evident in HMW1 and HMW2 mutants. The P41 mutant exhibits a terminal organelle detachment phenotype and lacked the bowl element normally present at the terminal organelle base. Complementation restored this substructure, establishing P41 as either a component of the bowl element or required for its assembly or stability, and that this bowl element is essential to anchor the terminal organelle but not for leverage in gliding. Mutants II‐3, III‐4 and topJ exhibited a visibly lower density of protein knobs on the terminal organelle surface. Mutants II‐3 and III‐4 lack accessory proteins required for a functional adhesin complex, while the topJ mutant lacks a DnaJ‐like co‐chaperone essential for its assembly. Taken together, these observations expand our understanding of the roles of certain terminal organelle proteins in the architecture and function of this complex structure.     

Apicoplast: keep it or leave it

Most Apicomplexans possess a relic plastid named apicoplast, originating from secondary endosymbiosis of a red algae. This non-photosynthetic organelle fulfils important metabolic functions and confers sensitivity to antibiotics. The tasks of this organelle is compared across the phylum of Apicomplexa, highlighting its role in metabolic adaptation to different intracellular niches     

Membrane trafficking and organelle biogenesis in Giardia lamblia: use it or lose it

The secretory transport capacity of Giardia trophozoites is perfectly adapted to the changing environment in the small intestine of the host and is able to deploy essential protective surface coats as well as molecules which act on epithelia. These lumen-dwelling parasites take up nutrients by bulk endocytosis through peripheral vesicles or by receptor-mediated transport. The environmentally-resistant cyst form is quiescent but poised for activation following stomach passage. Its versatility and fidelity notwithstanding, the giardial trafficking systems appear to be the product of a general secondary reduction process geared towards minimization of all components and machineries identified to date. Since membrane transport is directly linked to organelle biogenesis and maintenance, less complexity also means loss of organelle structures and functions. A case in point is the Golgi apparatus which is missing as a steady-state organelle system. Only a few basic Golgi functions have been experimentally demonstrated in trophozoites undergoing encystation. Similarly, mitochondrial remnants have reached a terminally minimized state and appear to be functionally restricted to essential iron-sulfur protein maturation processes. Giardia’s minimized organization combined with its genetic tractability provides unique opportunities to study basic principles of secretory transport in an uncluttered cellular environment. Not surprisingly, Giardia is gaining increasing attention as a model for the investigation of gene regulation, organelle biogenesis, and export of simple but highly protective cell wall biopolymers, a hallmark of all perorally transmitted protozoan and metazoan parasites.     

The New Face of the Lipid Droplet: Lipid Droplet Proteins

The lipid droplet (LD) is an organelle with vital functions found in nearly all organisms. LD proteomic research has provided fundamentally important insights into this organelle's functions. The review provides a summary of LD proteomic studies conducted across diverse organisms and cell and tissue types. The accumulated proteomic data are reviewed for evidence of a protein targeting mechanism for the organelle. The hypotheses for several specific localization mechanisms based on what is known about targeting mechanisms for other organelles and vesicles are provided. Although the nature of the mechanism is not known, the functional data demonstrate that the targeting mechanism and, indeed, the organelle itself, is conserved from prokaryotes to eukaryotes. It is hoped that the review will help inspire further research leading to novel discoveries in the field.     

Regulated exocytosis: new organelles for non-secretory purposes

Regulated exocytosis is a process in which the membranes of cytoplasmic organelles fuse with the plasma membrane in response to stimulation. In many cases (secretory exocytoses), the process functions to secrete specific products that are segregated in the organelle lumen (for example, neurotransmitters, hormones and enzymes) to the extracellular space. In other cases ('non-secretory exocytoses'), it functions to transfer the organelle membrane and its components to the cell surface. Here, the general properties of non-secretory exocytoses are discussed.     

Investigation of Peroxisome Biogenesis Revealed Possible New Roles for Autophagy Components

Precursor aminopeptidase I oligomerizes in the cytosol and is imported into the vacuole as a dodecamer via the cytoplasm-to-vacuole targeting (Cvt) pathway or autophagy. However, this is not the only example for the import of oligomeric protein complexes into an organelle. During peroxisome biogenesis folded and oligomeric proteins can be imported into the lumen of the organelle. The mechanism of this transport is still unknown. In this article, we point out mechanistic parallels between peroxisome biogenesis and the Cvt pathway or autophagy. Furthermore, we summarize our recently published investigation on a possible overlap between these pathways. Our investigation revealed new insights into autophagy and the Cvt pathway and possible new functions of Cvt4p, Cvt8p and Atg14p in organelle biogenesis or stability.

Addendum to:

Topogenesis of peroxisomal proteins does not require a functional cytoplasm-to-vacuole transport

Ines Heiland and Ralph Erdmann

Eur J Cell Biol 2005; 84:799-807     

Cytoplasmic organelles on the road to mRNA decay

Localization of both mRNAs and mRNA decay factors to internal membranes of eukaryotic cells provides a means of coordinately regulating mRNAs with common functions as well as coupling organelle function to mRNA turnover. The classic mechanism of mRNA localization to membranes is the signal sequence-dependent targeting of mRNAs encoding membrane and secreted proteins to the cytoplasmic surface of the endoplasmic reticulum. More recently, however, mRNAs encoding proteins with cytosolic or nuclear functions have been found associated with various organelles, in many cases through unknown mechanisms. Furthermore, there are several types of RNA granules, many of which are sites of mRNA degradation; these are frequently found associated with membrane-bound organelles such as endosomes and mitochondria. In this review we summarize recent findings that link organelle function and mRNA localization to mRNA decay. This article is part of a Special Issue entitled: RNA Decay mechanisms.     

The unusual mitochondrial compartment of Cryptosporidium parvum

Recent studies, including the Cryptosporidium parvum Genome Project, have provided evidence for a mitochondrial-derived compartment in this parasite. This organelle appears to lack a genome, and thus must be entirely dependent on nuclear-encoded proteins. Here, we review the evidence for such an organelle in C. parvum and its probable function. There is no adequate treatment for infection by this parasite and so the elucidation of the role of this organelle and the effective targeting of its functions by antimicrobial agents might provide new treatments for infection by C. parvum.     

Diversity and reductive evolution of mitochondria among microbial eukaryotes

All extant eukaryotes are now considered to possess mitochondria in one form or another. Many parasites or anaerobic protists have highly reduced versions of mitochondria, which have generally lost their genome and the capacity to generate ATP through oxidative phosphorylation. These organelles have been called hydrogenosomes, when they make hydrogen, or remnant mitochondria or mitosomes when their functions were cryptic. More recently, organelles with features blurring the distinction between mitochondria, hydrogenosomes and mitosomes have been identified. These organelles have retained a mitochondrial genome and include the mitochondrial-like organelle of Blastocystis and the hydrogenosome of the anaerobic ciliate Nyctotherus. Studying eukaryotic diversity from the perspective of their mitochondrial variants has yielded important insights into eukaryote molecular cell biology and evolution. These investigations are contributing to understanding the essential functions of mitochondria, defined in the broadest sense, and the limits to which reductive evolution can proceed while maintaining a viable organelle.     

Molecular characterization of the endoplasmic reticulum: insights from proteomic studies

The endoplasmic reticulum (ER) is a multifunctional intracellular organelle responsible for the synthesis, processing and trafficking of a wide variety of proteins essential for cell growth and survival. Therefore, comprehensive characterization of the ER proteome is of great importance to the understanding of its functions and has been actively pursued in the past decade by scientists in the proteomics field. This review summarizes major proteomic studies published in the past decade that focused on the ER proteome. We evaluate the data sets obtained from two different organs, liver and pancreas each of which contains a primary cell type (hepatocyte and acinar cell) with specialized functions. We also discuss how the nature of the proteins uncovered is related to the methods of organelle purification, organelle purity and the techniques used for protein separation prior to MS. In addition, this review also puts emphasis on the biological insights gained from these studies regarding the molecular functions of the ER including protein synthesis and translocation, protein folding and quality control, ER-associated degradation and ER stress, ER export and membrane trafficking, calcium homeostasis and detoxification and drug metabolism.     

Life and death of a BiP substrate

BiP is the mammalian endoplasmic reticulum (ER) Hsp70 orthologue that plays a major role in all functions of this organelle including the seemingly opposing functions of aiding the maturation of unfolded nascent proteins and identifying and targeting chronically unfolded proteins for degradation. The recent identification of mammalian BiP co-factors combined with delineation of the ER degradation machinery and data suggesting that the ER is subdivided into unique regions helps explain how these different functions can occur in the same organelle and raises some unresolved issues.     

Organelle communication: Signaling crossroads between homeostasis and disease

Cellular organelles do not function as isolated or static units, but rather form dynamic contacts between one another that can be modulated according to cellular needs. The physical interfaces between organelles are important for Ca²⁺ and lipid homeostasis, and serve as platforms for the control of many essential functions including metabolism, signaling, organelle integrity and execution of the apoptotic program. Emerging evidence also highlights the importance of organelle communication in disorders such as Alzheimer's disease, pulmonary arterial hypertension, cancer, skeletal and cardiac muscle dysfunction. Here, we provide an overview of the current literature on organelle communication and the link to human pathologies.