Mitochondrial protein translocases for survival and wellbeing

Sokòl, Anna M.; Sztolsztener, Malgorzata E.; Wasilewski, Michał; Heinz, Eva; Chacińska, Agnieszka

doi:10.1016/j.febslet.2014.05.028

Cited by 95 publications

(72 citation statements)

References 137 publications

(253 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Indeed, import of nuclear-encoded mitochondrial proteins is strongly correlated with indexes of biogenesis (149), and defects in the pathway are a cause of disease (59,151). Thus it is possible that alterations in aged muscle arising in the protein-import process could underlie mitochondrial dysfunction.…”

Section: Mitochondrial Protein Import and Agingmentioning

confidence: 99%

Mitochondria, Muscle Health, and Exercise with Advancing Age

2015

View full text Add to dashboard Cite

Skeletal muscle health is dependent on the optimal function of its mitochondria. With advancing age, decrements in numerous mitochondrial variables are evident in muscle. Part of this decline is due to reduced physical activity, whereas the remainder appears to be attributed to age-related alterations in mitochondrial synthesis and degradation. Exercise is an important strategy to stimulate mitochondrial adaptations in older individuals to foster improvements in muscle function and quality of life.Heather N. Carter, Chris C. W. The process of aging exploits the malleable nature of skeletal muscle. The age-related loss of muscle mass was termed sarcopenia, based on the Greek (sarx, flesh) and (penia, poverty) in 1988 (139). Accompanying this loss are profound architectural and molecular changes that alter muscle quality and are manifested in functional limitations. Decreases in muscle fiber number as well as fiber cross-sectional area are both contributing factors to sarcopenia (92) and consequently adversely affect force production (strength) (46, 63) and endurance of the older individual (12). Muscle mass typically peaks in the mid-20s (12, 34,92), and thereafter several distinct phases of muscle loss have been identified. In the third to fifth decade of life, a slow rate of muscle mass loss is noted, amounting to ϳ10% in total (34,92). In later adulthood (Ͼ45 yr), the rate of muscle loss increases, with appraisals ranging between 0.5 and 1.4% per year (12, 34,69). Even more dramatic changes are noted beyond the sixth decade of life. Along with the functional impairments imposed by sarcopenia, are the associated escalations in health care costs, along with coincident rises in metabolic diseases (e.g., Type 2 diabetes, obesity) and a greater risk of falls (67). In the U.S., it is expected that those 65 years of age and over will comprise ϳ20% of the population, or ϳ72 million people, by the year 2030 (20). Since the proportion of older adults is increasing, continued research into the mechanisms of muscle loss is warranted, along with the investigation of therapeutic strategies that can mitigate muscle atrophy during aging. Mitochondria have been implicated as potential mediators of sarcopenia. Recently, it has been suggested that dysfunction of these organelles can be considered a feature of aging (105). However, considerable controversy exists regarding the extent to which muscle mitochondria may be dysfunctional with aging, and thereby contribute to the loss of this tissue. Thus the purpose of this review is to examine the literature with respect to mitochondrial content and function in muscle with advancing age, and provide a perspective on the effectiveness of endurance/aerobic exercise as an intervention for mitochondrial biogenesis and muscle homeostasis in older individuals. Structural Features of Muscle Relevant to SarcopeniaIn young, healthy individuals, skeletal muscle comprises ϳ40% of total body mass and is important for locomotion and whole body metabolism. Myosin ATPase histochemistry and electrop...

show abstract

Section: Mitochondrial Protein Import and Agingmentioning

confidence: 99%

Mitochondria, Muscle Health, and Exercise with Advancing Age

2015

View full text Add to dashboard Cite

show abstract

“…3B; supplemental Table S13E, S13H, and S13I). Tom40p and Sam50p are core components of general translocase of the outer membrane (TOM) and sorting and assembly machinery (SAM), respectively (57). These two proteins were more abundant in both Kluyveromyces species (Fig.…”

Section: Species-specific Differentially Expressed Proteins In Both Kmentioning

confidence: 99%

Yeast Interspecies Comparative Proteomics Reveals Divergence in Expression Profiles and Provides Insights into Proteome Resource Allocation and Evolutionary Roles of Gene Duplication

Kito

Ito

Nohara

et al. 2016

Molecular & Cellular Proteomics

View full text Add to dashboard Cite

Omics analysis is a versatile approach for understanding the conservation and diversity of molecular systems across multiple taxa. In this study, we compared the proteome expression profiles of four yeast species (Saccharomyces cerevisiae, Saccharomyces mikatae, Kluyveromyces waltii, and Kluyveromyces lactis) grown on glucose-or glycerol-containing media. Conserved expression changes across all species were observed only for a small proportion of all proteins differentially expressed between the two growth conditions. Two Kluyveromyces species, both of which exhibited a high growth rate on glycerol, a nonfermentative carbon source, showed distinct species-specific expression profiles. In K. waltii grown on glycerol, proteins involved in the glyoxylate cycle and gluconeogenesis were expressed in high abundance. In K. lactis grown on glycerol, the expression of glycolytic and ethanol metabolic enzymes was unexpectedly low, whereas proteins involved in cytoplasmic translation, including ribosomal proteins and elongation factors, were highly expressed. These marked differences in the types of predominantly expressed proteins suggest that K. lactis optimizes the balance of proteome resource allocation between metabolism and protein synthesis giving priority to cellular growth. In S. cerevisiae, about 450 duplicate gene pairs were retained after whole-genome duplication. Intriguingly, we found that in the case of duplicates with conserved sequences, the total abundance of proteins encoded by a duplicate pair in S. cerevisiae was similar to that of protein encoded by nonduplicated ortholog in Kluyveromyces yeast. Genome-wide analysis of multiple organisms is one of the most useful approaches to uncover both the conservation and divergence of biological processes with respect to evolutionary history. Transcriptomic studies using DNA microarrays or deep-sequencing techniques have not only characterized the expression profiles of cell-type and -state specific genes involved in many biological processes, the have also revealed the expression patterns of genes involved in a variety among different species (1). Proteomic analysis, for which mass spectrometry is one of the most powerful and widely used analytical techniques (2), can provide much more direct evidence of both conservation and divergence of expression profiles across multiple species.Interspecies comparative proteomic studies with mass spectrometry have been hitherto carried out in primates (3, 4), yeasts (5), and a variety of other model organisms (6 -9). Abundance of the core proteome, for which orthologs have been identified in all organisms investigated, are well conserved across a wide range model organisms, including yeasts, plants, worms, flies, and humans (7). The profiles of orthologous protein abundance appear to be more conserved than profiles of transcript abundance in chimpanzees and humans (4), worms and flies (6), and many other prokaryotes and eukaryotes (8), suggesting that there is more selection pressure on protein expression than transcript e...

show abstract

“…It is now evident that most of our understanding of the mitochondrial protein import process has been derived from studies in the yeast system and there has been considerable advance in the understanding of how nuclear-encoded precursor proteins are translocated across and into the membranes of mitochondria (Schulz et al, 2015;Sokol et al, 2014). Human mitochondria translocation machineries were being thought to be similar to that of yeast (Bauer et al., 1999).…”

Section: Human Mitochondrial Protein Transport -An Enigmamentioning

confidence: 99%

Post Genomics Identification of Blood Stage Invasins of Plasmodium Falciparum

Chauhan¹

2017

Proceedings of the Indian National Science Academy

View full text Add to dashboard Cite

Human mitochondria require ~1500 proteins for its constitutive functions. However, the mitochondrial genome is gene deficient and most of the mitochondrial proteome is nuclear encoded and transported into the organelle. Import of majority of mitochondrial proteome is mediated by presequence pathway and requires functional interplay between a subset of molecular chaperones, along with accessory factors. Although detailed analysis has been carried out in yeast system, our understanding of human mitochondrial proteome maintenance has been severely limited by the absence of significant structural and functional information on the organization TIM23 complex in humans. Recent studies have revealed the presence of multiple presequence translocases in human mitochondria that show considerable diversity in their substrate and physiological specificity. The core organization and inter-molecular interactions between these machineries seems to be evolutionary conserved. These translocases have principally diversified due to divergence of Hsp70 co-chaperones and channel component Tim17. Another important feature associated with human mitochondrial translocases, which in most cases are absent in lower eukaryotes, is its multifunctionality. Other than housekeeping protein import, human mitochondrial translocases have gained secondary functions such asinvolvment in ROS sensing and regulation of redox balance, modulation of cellular sensitivity to xenobiotic drugs, maintenance of mitochondrial DNA, assembly of respiratory complexes' and import of non-canonical mitochondrial substrates. The origin of multifunctionality is indicative towards the possibility of functional connections between mitochondrial protein import and regulation of cellular pathways; hence, opening up new avenues of future research. Keywords IntroductionMitochondria are endosymbiotic cellular organelle enclosed in double membrane and form an integral part of eukaryotic cells. The word mitochondrion comes from the Greek ìßôïò, mitos, i.e. "thread", and ÷ïíäñßïí, chondrion, i.e. "granule". The term "mitochondria" was coined by Carl Benda in 1898 (cited in Margulis, 1970). Benjamin F. Kingsbury (1912) first related these organelles with cell respiration (cited in Sagan, 1967), followed by Otto Heinrich Warburg (Ernster and Schatz, 1981; Gray et al., 1999). In addition to supplying cellular energy, mitochondria are involved in other tasks such as signaling, cellular differentiation, cell death, as well as the control of the cell cycle and cell growth (Gray et al., 1999). Mitochondria have been implicated in several human diseases, including mitochondrial disorders and cardiac dysfunction, and may play a role in the aging process (Fulda et al., 2010; Gulbins et al., 2003; Hayashi et al., 2009; Kroemer, 2006; Lesnefsky et al., 2001; McBride et al., 2006).Mitochondrial genomes are very small and show a great deal of variation as a result of divergent evolution (Ernster and Schatz, 1981; Henze and Martin, 2003; Peng et al., 2005). The human mitochondrial geno...

show abstract

Mitochondrial protein translocases for survival and wellbeing

Cited by 95 publications

References 137 publications

Mitochondria, Muscle Health, and Exercise with Advancing Age

Mitochondria, Muscle Health, and Exercise with Advancing Age

Yeast Interspecies Comparative Proteomics Reveals Divergence in Expression Profiles and Provides Insights into Proteome Resource Allocation and Evolutionary Roles of Gene Duplication

Post Genomics Identification of Blood Stage Invasins of Plasmodium Falciparum

Contact Info

Product

Resources

About