Mitochondrial Turnover and Aging of Long-Lived Postmitotic Cells: The Mitochondrial–Lysosomal Axis Theory of Aging

摘要: It is now generally accepted that aging and eventual death of multicellular organisms to a large extent related macromolecular damage by mitochondrially produced reactive oxygen species, mostly affecting long-lived postmitotic cells, such as neurons cardiac myocytes. These cells are rarely or not at all replaced during life can be old the whole organism. The inherent inability autophagy other cellular-degradation mechanisms remove damaged structures completely results in progressive accumulation garbage, including cytosolic protein aggregates, defective mitochondria, lipofuscin, an intralysosomal indigestible material. In this review, we stress importance crosstalk between mitochondria lysosomes aging. slow lipofuscin within seems depress autophagy, resulting reduced turnover effective mitochondria. latter only functionally deficient but also produce increased amounts prompting lipofuscinogenesis. Moreover, enlarged poorly autophagocytosed constitute growing population badly functioning organelles do fuse exchange their contents with normal progress these changes result enhanced oxidative stress, decreased ATP production, collapse cellular catabolic machinery, which eventually incompatible survival.