Mitochondria have long been implicated in aging. Most research linking this organelle to aging has stressed the deleterious effects of ROS generated by mitochondria during the course of aging, often hinting at the self-accelerating aspects of this phenomenon. However, it has become clear over the past decade that compensatory cell responses can attenuate the consequences of mitochondrial dysfunction occurring during aging. One of these adaptive responses is the retrograde response, which we demonstrated in yeast allows the cell to live as long as it does (14). This mechanism is now known to operate at the organism level in C. elegans as well (6-7), and evidence for its operation in human cells has been presented (8-10, 21). More recent work has pointed to mitochondrial quality control as an important device mitigating the accumulation of damage to mitochondria, either through intrinsic mechanisms (19-20, 22) or through mitophagy (23). The significance of this quality control for maintenance of age asymmetry between mother and daughter yeast cells is clear (19-20, 24), and it has implications for stem cell aging. The convergence of the retrograde response and mitochondrial quality control and evidence that sphingolipid signaling is involved are exciting new developments (25-26) (Fig. 14).

National Institute of Health (NIH)
Method to Extend Research in Time (MERIT) Award (R37)
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Guo, Max
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Tulane University
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Malik, Deepika; Hsu, Tiffany; Falatoonzadeh, Payam et al. (2014) Human retinal transmitochondrial cybrids with J or H mtDNA haplogroups respond differently to ultraviolet radiation: implications for retinal diseases. PLoS One 9:e99003
Jazwinski, S Michal (2014) The retrograde response: a conserved compensatory reaction to damage from within and from without. Prog Mol Biol Transl Sci 127:133-54
Kenney, M Cristina; Chwa, Marilyn; Atilano, Shari R et al. (2014) Inherited mitochondrial DNA variants can affect complement, inflammation and apoptosis pathways: insights into mitochondrial-nuclear interactions. Hum Mol Genet 23:3537-51
Kenney, M Cristina; Chwa, Marilyn; Atilano, Shari R et al. (2014) Molecular and bioenergetic differences between cells with African versus European inherited mitochondrial DNA haplogroups: implications for population susceptibility to diseases. Biochim Biophys Acta 1842:208-19
Jazwinski, S Michal (2013) The retrograde response: when mitochondrial quality control is not enough. Biochim Biophys Acta 1833:400-9
Kenney, M Cristina; Chwa, Marilyn; Atilano, Shari R et al. (2013) Mitochondrial DNA variants mediate energy production and expression levels for CFH, C3 and EFEMP1 genes: implications for age-related macular degeneration. PLoS One 8:e54339
Srinivasan, Visish; Kriete, Andres; Sacan, Ahmet et al. (2010) Comparing the yeast retrograde response and NF-?B stress responses: implications for aging. Aging Cell 9:933-41
Wang, Jinqing; Jiang, James C; Jazwinski, S Michal (2010) Gene regulatory changes in yeast during life extension by nutrient limitation. Exp Gerontol 45:621-31
Ponnusamy, Suriyan; Alderson, Nathan L; Hama, Hiroko et al. (2008) Regulation of telomere length by fatty acid elongase 3 in yeast. Involvement of inositol phosphate metabolism and Ku70/80 function. J Biol Chem 283:27514-24
Senkal, Can E; Ponnusamy, Suriyan; Rossi, Michael J et al. (2007) Role of human longevity assurance gene 1 and C18-ceramide in chemotherapy-induced cell death in human head and neck squamous cell carcinomas. Mol Cancer Ther 6:712-22

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