Speaker: Chuankai (Kai) Zhou, Ph.D.(BS'06), Assistant Professor, Buck Institute for Research on Aging

Time: 10:00-11:30 a.m., Feb 18, 2025, GMT+8

Venue: Rm B101, Lui Che Woo Building, PKU  

Abstract: 

Loss of proteostasis is a fundamental hallmark of aging conserved from yeast to humans. Many age-related diseases are characterized by protein aggregation and diminished lysosomal function-key manifestations of declining protestasis. Our laboratory investigates the mechanisms of protestasis during stress and aging, with a particular emphasis on the role of mitochondria in these processes. We have found that ubiquitously distributed misfolded proteins do not aggregate randomly in vivo; rather, they are drawn to aggregation sites initiated by nascent mitochondrial proteins on the mitochondrial membrane via multivalent hydrophobic interactions. Beyond protein aggregation, our recent work reveals that mitochondria control lysosomal acidification through a previously unrecognized mechanism. Proper acidification is essential for optimal enzyme activity, intracellular signaling, and autophagy, and defects in this process are commonly linked to aging and cellular senescence. Age-dependent alterations in organelle contacts impair lysosome acidification in both yeast and human cells. These findings are part of our ongoing efforts to elucidate the interconnections among the various hallmarks of aging, such as mitochondrial dysfunction, loss of protestasis, and defect in lysosome/macroautophagy.

Source: School of Life Sciences, PKU