Involvement of Mortalin in Cellular Senescence from the Perspective of its Mitochondrial Import, Chaperone, and Oxidative Stress Management Functions

Research Institute for Cell Engineering, National Institute of Advanced Industrial Science and Technology (AIST), Central 4, 1-1-1 Higashi, Tsukuba, Ibaraki 305 8562, Japan.
Annals of the New York Academy of Sciences (Impact Factor: 4.31). 05/2007; 1100(1):306-11. DOI: 10.1196/annals.1395.032
Source: PubMed

ABSTRACT Mortalin (mtHSP70/GRP75) is a heat uninducible member of hsp70 family of proteins. Some of the established features of mortalin include its various subcellular sites, multiple binding partners, and differential subcellular distribution in normal and immortal cells. Overexpression of mortalin leads to extended life span in nematode and normal human cells. On the other hand, it serves as a major target for oxidation and was shown to be involved in old age pathologies including Parkinson's and Alzheimer's disease. Since mortalin interacts with many proteins, its modifications in response to stress and damage caused by intracellular oxidation are likely to generate pleiotropic effects. For example, (a) inefficient import of mitochondrial proteins by mortalin-Tim complexes may result into inefficient mitochondrial genesis, energy generation, and functional decline and (b) inefficient chaperoning of proteins can result into a garbage catastrophe.

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    • "Changes in autophagy and mitochondrial morphology are also suggested by the decrement of PARK7 and HSPA9 in the early phase. The latter is a part of the mitochondrial inner membrane transporter (TIM) complex [26] and in association with PARK7, plays "
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    Proteomics 01/2015; 15(1). DOI:10.1002/pmic.201400306 · 3.97 Impact Factor
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    • "Glucoseregulated protein 75 (GRP75, also called mortalin/ mtHSP70/mot-2), a member of the cytoprotective Hsp70 family of chaperons, interacts with both PINK1 (Jin et al. 2006, 2007; Li et al. 2005; Rakovic et al. 2011) and DJ-1 (Jin et al. 2005; Li et al. 2005). GRP75 is mainly localized within the mitochondria matrix of neurons where it accomplishes several functions such as mitochondrial import and oxidative stress management (Yaguchi et al. 2007). Overexpression of GRP75 leads to extended life span in nematodes and human cells. "
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    • "Mortalin resides in multiple cellular locations that include the endoplasmic reticulum, cytoplasmic vesicles, and the cytosol, but primarily is found in mitochondria. Moreover, mortalin has been associated with multiple functions, including intracellular trafficking , antigen processing, regulation of cell proliferation, aging, differentiation and tumorigenesis [1] [2] [9], while also interacting with many other partner proteins, including Tim44 in the mitochondrial protein import machinery [10] [11]. "
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