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Mitochondrial Dysfunction in Chronic Disease
Published in Peter M. Tiidus, Rebecca E. K. MacPherson, Paul J. LeBlanc, Andrea R. Josse, The Routledge Handbook on Biochemistry of Exercise, 2020
Christopher Newell, Heather Leduc-Pessah, Aneal Khan, Jane Shearer
Separating the intermembrane space from the cytosol, the OMM is responsible for the exchange of information between the mitochondria and the cell. Embedded in the OMM are large numbers of voltage-dependent anion channel (VDAC) proteins, which regulate metabolic and energetic flux across the OMM (15). VDAC proteins maintain metabolic homeostasis by shuttling ATP, ADP, metabolites, and various enzymes, including creatine kinase and hexokinase, across the OMM (15). Larger proteins migrating from the cytosol into the mitochondria must enter through a translocase of the outer membrane (TOM) protein complex (57). In dysfunctional mitochondria, VDAC proteins play an important role in apoptosis through OMM permeabilization and release of cytochrome c (41). Specific to regulation of calcium signalling, the OMM is known to share structures with the endoplasmic reticulum (ER). The mitochondria-associated membranes (MAMs) are connections between the mitochondria and ER, which act as a signalling and metabolic interface (14, 26). In functional mitochondria, the MAMs maintain calcium homeostasis, lipid synthesis, and mitochondrial biogenesis (136). However, various stress response signals released by either the ER or dysfunctional mitochondria can initiate OMM permeabilization and apoptosis (136).
Mitochondrial Dysfunction in Chronic Kidney Disease
Published in Shamim I. Ahmad, Handbook of Mitochondrial Dysfunction, 2019
Maria V. Irazabal, Alfonso Eirin
Recent studies suggest that deficiency of PC1 is associated with impaired mitochondrial calcium uptake (Padovano et al. 2016) due to alterations in the expression of mitochondria associated membranes, which regulate physiological functions between ER and mitochondria (Patergnani et al. 2011). Interestingly, the cAMP-protein kinase-A (PKA) complex phosphorylates the translocase of the outer membrane complex (Schmidt et al. 2011), impairing the import of metabolite carriers. However, whether the increase in cAMP-PKA signaling observed PKD is associated defective protein import remains to be elucidated.
Passive heat stress induces mitochondrial adaptations in skeletal muscle
Published in International Journal of Hyperthermia, 2023
Erik D. Marchant, W. Bradley Nelson, Robert D. Hyldahl, Jayson R. Gifford, Chad R. Hancock
Aside from the apparent role of HSP72 in activating PGC-1α through AMPK and SIRT1, heat shock proteins play a vital role in the import of nuclear-encoded mitochondrial proteins into the mitochondrial matrix, as well as in helping fold and assemble them into complexes [52]. The mitochondrial proteome is composed of over 1,000 proteins, 99% of which are nuclear encoded, with only 13 being coded for by mitochondrial DNA [80]. Because most mitochondrial proteins are translated outside the mitochondria, specialized import machinery is required to introduce newly synthesized proteins into the mitochondrial matrix. Two primary players in this process are the translocase of the outer membrane (TOM), and the translocase of the inner membrane (TIM) [81]. Interestingly, both cytosolic and mitochondrial heat shock proteins are vital for this translocation process, partially due to their interactions with TIM and TOM [81–83]. Furthermore, once introduced into the mitochondria, heat shock protein 60 is necessary for the proper folding and assembly of the respiratory complexes of the electron transport system [84]. To date, it is unknown if passive heating in humans or animals improves protein import and folding due to increased HSP content or activation in skeletal muscle. However, the vital role of HSPs in mitochondrial protein import and assembly suggests that this is an important area for future research.
Omentin-1 promotes mitochondrial biogenesis via PGC1α-AMPK pathway in chondrocytes
Published in Archives of Physiology and Biochemistry, 2023
Zhigang Li, Yao Zhang, Fengde Tian, Zihua Wang, Haiyang Song, Haojie Chen, Baolin Wu
The mitochondrion is the "powerhouse" in eukaryotic cells. Mitochondrial biogenesis is the process of increasing cellular metabolic capacity, featured with the synthesis of enzymes for both glycolysis and oxidative phosphorylation (Jornayvaz and Shulman 2010). An efficient mitochondrial biogenesis needs the import of nuclear protein as well as mitochondrial replication, mitochondrial fusion and fission (Nunnari and Suomalainen 2012). Mitochondria in mammalian cells contain more than 1500 proteins, but only 13 proteins are coded in mitochondrial DNA, a majority of them are synthesised from nuclear DNA coding genes. Various mitochondrial molecular markers are used to study the mitochondrial regulation in eukaryotes. Translocase of the outer membrane (TOM) complex is a membrane-bound translocator vital to import mitochondrial precursors, and TOM complex includes several subunits including TOM20, TOM40 and TOM70 and is secured by TOM5, TOM6, TOM7, etc. (Ahting et al.1999). Several subunits of mitochondrial ATP synthases are also used as the markers of functional mitochondria, including ATPA, ATP5C1, ATPD and other subunits. The electron transport chain (ETC) located within the mitochondrial inner membrane composes of four protein complexes. Succinate dehydrogenase complex iron-sulfur subunit B (SDHB) links the pathways of Krebs cycle and oxidative phosphorylation. Mitochondrial DNA encoded subunits (MTCO1, MTCO2, MTCO3) are important subunits of complex IV (Zhao et al.2019).
Gut bacteria signaling to mitochondria in intestinal inflammation and cancer
Published in Gut Microbes, 2020
Dakota N. Jackson, Arianne L. Theiss
Mitochondria are double membrane-bound organelles found generally in large numbers in the cytoplasm of eukaryotic cells. Mitochondria are important organelles due to their primary function to generate energy for the cell in the form of adenosine 5′-triphosphate (ATP). In 1957, Phillip Skiekevitz coined the phrase “powerhouse of the cell” for the organelle. In addition to ATP production, mitochondria are an important site of intracellular calcium storage and the induction of apoptosis during cellular stress predominantly by the release of cytochrome c into the cytosol. The outer mitochondrial membrane (OMM) is composed of a phospholipid bilayer separating the mitochondria and its contents from the cytosol. Ions and proteins smaller than 5 kDa diffuse into and out of the mitochondria freely via porins, and therefore, the concentration of small proteins and ions in the mitochondrial intermembrane space matches the cytosol. Proteins larger than 5 kDa possessing a 5′ mitochondrial localization sequence translocate across the OMM via binding to translocase of the outer membrane (TOM) transporters. Proteins transferred into the mitochondria include nuclear DNA encoded proteins such as those for oxidative phosphorylation and heat shock proteins.1 The inner mitochondrial membrane (IMM) is also a phospholipid bilayer and houses electron transport chain (ETC) complexes which drive ATP production. Transporters called translocase of the inner membrane (TIMs) are required for all ions and proteins to enter the mitochondrial matrix2 allowing formation of the protein gradient in the space between the OMM and IMM, driving electron flow through the ETC.3 Inward folds of the IMM are called cristae, which increase the surface area for ATP production to match cellular demand.4 Within the IMM is the mitochondrial matrix which houses ribosomes, mitochondrial DNA (mtDNA), and ATP synthase proteins that facilitate the catalysis from adenosine diphosphate (ADP) to ATP.1