Mitochondrial Hsp70 plays a critical role in maintenance of mitochondrial life cycle in Saccharomyces cerevisiae Vinaya Vishwanathan1, Divya.P1 and Patrick D'Silva1* 1Department of Biochemistry, Indian Institute of Science, Bangalore -560012, India *Corresponding Author.
Mitochondrial Hsp70 (mtHsp70) maintains protein quality control by regulating the import and folding of several proteins in the mitochondria. An additional quality check occurs at the organelle level via the process of mitophagy. The two events are critical for the maintenance of mitochondrial homeostasis, since disruption of these processes has been implicated in ageing, including several human diseases like cancer and neurodegenerative disorders. Studies on an mtHsp70 mutant (P509S) associated with Parkinson's disease; indicate an altered chaperone function owing to an enhanced interaction with its J-protein partner (mtHsp40). The mitochondrial stress due to the loss of chaperone function is alleviated upon increased mitophagy suggesting an overlay between mitochondrial quality control pathways. However, how the two quality checkpoints converge to ensure mitochondrial homeostasis, still remains to be explored. Utilizing biochemical and yeast genetic approaches, we provide evidence to demonstrate a cross-talk between mtHsp70 and mitophagy in the maintenance of mitochondrial homeostasis. In yeast, upon the abrogation of mitophagy, Ssc1 (mtHsp70) mutants exhibit altered mitochondrial content and morphology, owing to a perturbation in the organelle dynamics. Further, these mutants also display increased oxidative stress, reduced lifespan and signs of early apoptosis. In summary, our findings provide a first-time insight into the critical roles of Ssc1, mitochondrial dynamics and turnover in the maintenance of mitochondrial form and function in yeast.
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