Molecular chaperones and the biogenesis of mitochondria and peroxisomes

Summary— A review of the proteinaceous machinery involved in protein sorting pathways and protein folding and assembly in mitochondria and peroxisomes is presented. After considering the various sorting pathways and targeting signals of mitochondrial and peroxisomal proteins, we make a comparative dissection of the protein factors involved in: i) the stabilization of cytosolic precursor proteins in a translocation competent conformation; ii) the membrane import apparatus of mitochondria and peroxisomes; iii) the processing of mitochondrial precursor proteins, and the eventual processing of certain peroxisomal precursor, in the interior of the organelles; and iv) the requirement of molecular chaperones for appropriate folding and assembly of imported proteins in the matrix of both organelles. Those aspects of mitochondrial biogenesis that have developed rapidly during the last few years, such as the requirement of molecular chaperones, are stressed in order to stimulate further parallel investigations aimed to understand the origin, biochemistry, molecular biology and pathology of peroxisomes. In this regard, a brief review of findings from our group and others is presented in which the role of the F₁-ATPase α-subunit is pointed out as a molecular chaperone of mitochondria and chloroplasts. In addition, data are presented that could question our previous indication that the immunoreactive protein found in the rat liver peroxisomes is due to the presence of the F₁-ATPase α-subunit.     

The Role of Cellular and Extracellular Matrix Adhesion Proteins in Organ Transplantation

The specific adhesion of cells to other cells or to particular tissue microenvirorvments is a basic function of cell migration and recognition, and underlines many biologic processes including embryogenesis, repair and immunity. Leukocytes express an array of surface receptors broadly known as “accessory adhesion molecules.” which mediate most cell -cell interactions, direct lymphocyte traffic between anatomical compartments, and facilitate cellular adhesion to the inflammation or alloantigenic sites (Springer 1990). In addition, adhesion molecules are involved in the process of antigen recognition, and may costimulate cell activation and transformation. These proteins are thought to affect the very early antigen independent events between host leukocytes and vascular endothelium. Because of these activities, the subject of adhesion molecules is gaining interest in the field of organ transplantation, in both conceptualization and development of novel therapeutic strategies (de Sousa et al. 1991, Kupiec-Weglinski et al. 1993a, Heemann et al. 1993).     

Cell Cycle Arrest of Proliferating Neuronal Cells by Serum Deprivation Can Result in Either Apoptosis or Differentiation

Abstract: Apoptotic cell death plays a critical role in the development of the nervous system. The death of mature nondividing neurons that fail to receive appropriate input from the target field has been extensively studied. However, the mechanisms mediating the extensive cell death occurring in areas of the developing brain where proliferating neuroblasts differentiate into mature nondividing neurons have not been analyzed. We show here that the cell cycle arrest of a proliferating cell of neuronal origin by removal of serum results in either apoptotic cell death or differentiation to a mature nondividing neuronal cell. The proportion of cells undergoing death or differentiation is influenced in opposite directions by treatment of the cells with cyclic AMP and retinoic acid. This suggests that following the withdrawal of signals stimulating neuroblast cell division, neuronal cells either can cease to suppress a constitutive suicide pathway and hence die by apoptosis or, alternatively, can differentiate into a mature neuronal cell. Regulation of the balance between apoptosis and neuronal differentiation could therefore play a critical role in controlling the numbers of mature neurons that form.     

Relationships between cell surface protease and acid phosphatase activities ofLeishmania promastigote

A correlation between the ratio of the cell surface protease activity to phosphatase activity and the complexity of the pattern of cell surface exposed polypeptides ofLeishmania promastigotes was demonstrated for various strains grown under similar conditions. The ratio of the cell surface protease activity to acid phosphatase activity was high forL. major andL.b. panamensis and it correlates with the expression of a single polypeptide of 63 KDa on their cell surface. Intermediate and lower ratios of these enzymatic activites relate with more complex radio-iodinated patterns: two main bands inL.b. guyanensis (70 and 58 KDa) andL.b. braziliensis (72 and 60 KDa) and three main bands 65, 50, 27 KDa in allL.m. mexicana strains tested. Evidence is presented that the acid phosphatase located on theL.m. mexicana cell surface is not an artifact due to a secondary absorption of the secreted acid phosphatase from the culture medium. These results confirm theLeishmania antigen cell surface heterogeneity. The implications on the biology ofLeishmania and the clinical manifestation of leishmaniasis are discussed.     

Cryptophytes: An emerging algal group in the rapidly changing Antarctic Peninsula marine environments

The western Antarctic Peninsula (WAP) is a climatically sensitive region where foundational changes at the basis of the food web have been recorded; cryptophytes are gradually outgrowing diatoms together with a decreased size spectrum of the phytoplankton community. Based on a 11-year (2008–2018) in-situ dataset, we demonstrate a strong coupling between biomass accumulation of cryptophytes, summer upper ocean stability, and the mixed layer depth. Our results shed light on the environmental conditions favoring the cryptophyte success in coastal regions of the WAP, especially during situations of shallower mixed layers associated with lower diatom biomass, which evidences a clear competition or niche segregation between diatoms and cryptophytes. We also unravel the cryptophyte photo-physiological niche by exploring its capacity to thrive under high light stress normally found in confined stratified upper layers. Such conditions are becoming more frequent in the Antarctic coastal waters and will likely have significant future implications at various levels of the marine food web. The competitive advantage of cryptophytes in environments with significant light level fluctuations was supported by laboratory experiments that revealed a high flexibility of cryptophytes to grow in different light conditions driven by a fast photo-regulating response. All tested physiological parameters support the hypothesis that cryptophytes are highly flexible regarding their growing light conditions and extremely efficient in rapidly photo-regulating changes to environmental light levels. This plasticity would give them a competitive advantage in exploiting an ecological niche where light levels fluctuate quickly. These findings provide new insights on niche separation between diatoms and cryptophytes, which is vital for a thorough understanding of the WAP marine ecosystem.     

Tropical dry woodland loss occurs disproportionately in areas of highest conservation value

Tropical and subtropical dry woodlands are rich in biodiversity and carbon. Yet, many of these woodlands are under high deforestation pressure and remain weakly protected. Here, we assessed how deforestation dynamics relate to areas of woodland protection and to conservation priorities across the world's tropical dry woodlands. Specifically, we characterized different types of deforestation frontier from 2000 to 2020 and compared them to protected areas (PAs), Indigenous Peoples' lands and conservation areas for biodiversity, carbon and water. We found that global conservation priorities were always overrepresented in tropical dry woodlands compared to the rest of the globe (between 4% and 96% more than expected, depending on the type of conservation priority). Moreover, about 41% of all dry woodlands were characterized as deforestation frontiers, and these frontiers have been falling disproportionately in areas with important regional (i.e. tropical dry woodland) conservation assets. While deforestation frontiers were identified within all tropical dry woodland classes of woodland protection, they were lower than the average within protected areas coinciding with Indigenous Peoples' lands (23%), and within other PAs (28%). However, within PAs, deforestation frontiers have also been disproportionately affecting regional conservation assets. Many emerging deforestation frontiers were identified outside but close to PAs, highlighting a growing threat that the conserved areas of dry woodland will become isolated. Understanding how deforestation frontiers coincide with major types of current woodland protection can help target context-specific conservation policies and interventions to tropical dry woodland conservation assets (e.g. PAs in which deforestation is rampant require stronger enforcement, inactive deforestation frontiers could benefit from restoration). Our analyses also identify recurring patterns that can be used to test the transferability of governance approaches and promote learning across social–ecological contexts.