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The mitochondrial unfolded protein response (UPR mt) is a cellular stress response related to the mitochondria. The UPR mt results from unfolded or misfolded proteins in mitochondria beyond the capacity of chaperone proteins to handle them. [1] The UPR mt can occur either in the mitochondrial matrix or in the mitochondrial inner membrane. [1]
Mitochondrial genes are transcribed as multigenic transcripts, which are cleaved and polyadenylated to yield mature mRNAs. Most proteins necessary for mitochondrial function are encoded by genes in the cell nucleus and the corresponding proteins are imported into the mitochondrion. [144]
The translocase of the outer membrane (TOM) is a complex of proteins found in the outer mitochondrial membrane of the mitochondria. It allows movement of proteins through this barrier and into the intermembrane space of the mitochondrion. Most of the proteins needed for mitochondrial function are encoded by the nucleus of the cell.
The capacity for mitochondrial biogenesis has been shown to decrease with age, and such decreased mitochondrial function has been associated with diabetes and cardiovascular disease. [ 20 ] [ 21 ] [ 22 ] Aging and disease can induce changes in the expression levels of proteins involved in the fission and fusion mechanisms of mitochondria, thus ...
The unfolded protein response (UPR) is a cellular stress response related to the endoplasmic reticulum (ER) stress. [1] It has been found to be conserved between mammalian species, [2] as well as yeast [1] [3] and worm organisms.
Mitofusin-2 (MFN2) is a mitochondrial membrane protein that plays a central role in regulating mitochondrial fusion and cell metabolism. More specifically, MFN2 is a dynamin-like GTPase embedded in the outer mitochondrial membrane (OMM) which in turn affects mitochondrial dynamics, distribution, quality control, and function.
Once this protein is altered, there is a change in the cristae structure, release of cytochrome c, and the activation of the destructive caspase enzymes. These resulting changes indicate that inner mitochondrial membrane structure is linked with regulatory pathways in influencing cell life and death.
Diablo homolog (DIABLO) is a mitochondrial protein that in humans is encoded by the DIABLO (direct IAP binding protein with low pI) gene on chromosome 12. [5] [6] [7] DIABLO is also referred to as second mitochondria-derived activator of caspases or SMAC. This protein binds inhibitor of apoptosis proteins (IAPs), thus freeing caspases to ...