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PINK1-Parkin Pathway Activity Is Regulated by Degradation of PINK1 in the Mitochondrial Matrix

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Mitochondria are essential organelles that provide most of the cell's energy and perform many other critical functions. The gradual accumulation of defective mitochondria is thought to play a role in aging and in diseases of the nervous system, including Parkinson's disease. The selective elimination of defective mitochondria is therefore a vital task for the cell, and the protein PINK1 was recently identified as a critical player in this process. PINK1 accumulates on the surface of mitochondria after they are damaged, starting a process that leads ultimately to the elimination of defective mitochondria. Previous work indicated that PINK1 does not accumulate on healthy mitochondria because it is rapidly degraded. However, it was unclear exactly how and where this degradation occurred. Our work shows that Lon protease promotes the degradation of PINK1 in the mitochondrial matrix. This finding provides new insight into the mechanisms of mitochondrial quality control, and reveals a potential strategy for treating the many diseases associated with the accumulation of defective mitochondria.

Vyšlo v časopise: PINK1-Parkin Pathway Activity Is Regulated by Degradation of PINK1 in the Mitochondrial Matrix. PLoS Genet 10(5): e32767. doi:10.1371/journal.pgen.1004279
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1004279

Souhrn

Mitochondria are essential organelles that provide most of the cell's energy and perform many other critical functions. The gradual accumulation of defective mitochondria is thought to play a role in aging and in diseases of the nervous system, including Parkinson's disease. The selective elimination of defective mitochondria is therefore a vital task for the cell, and the protein PINK1 was recently identified as a critical player in this process. PINK1 accumulates on the surface of mitochondria after they are damaged, starting a process that leads ultimately to the elimination of defective mitochondria. Previous work indicated that PINK1 does not accumulate on healthy mitochondria because it is rapidly degraded. However, it was unclear exactly how and where this degradation occurred. Our work shows that Lon protease promotes the degradation of PINK1 in the mitochondrial matrix. This finding provides new insight into the mechanisms of mitochondrial quality control, and reveals a potential strategy for treating the many diseases associated with the accumulation of defective mitochondria.

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