Atg1-mediated autophagy suppresses tissue degeneration in mutants by promoting mitochondrial fission in .

Mitochondrial dysfunction is considered a hallmark of multiple neurodegenerative diseases, including Parkinson's disease (PD). The PD familial genes and function in a conserved pathway that regulates mitochondrial function, including dynamics (fusion and fission). Mammalian cell culture studies suggested that the pathway promotes mitophagy (mitochondrial autophagy). Mitophagy through mitochondrial fission and autolysosomal recycling was considered a quality control system at the organelle level. Whether defects in this quality control machinery lead to pathogenesis in vivo in PD remains elusive. Here, we found that elevating autophagy by overexpression can significantly rescue mitochondrial defects and apoptotic cell death in and mutants in . Surprisingly, the rescue effect relied both on the autophagy-lysosome machinery and on , a mitochondrial fission molecule. We further showed that Atg1 promotes mitochondrial fission by posttranscriptional increase in the Drp1 protein level. In contrast, increasing fission (by overexpression) or inhibiting fusion (by knocking down ) rescues mutants when lysosomal or proteasomal machinery is impaired. Taken together, our results identified Atg1 as a dual-function node that controls mitochondrial quality by promoting mitochondria fission and autophagy, which makes it a potential therapeutic target for treatment of mitochondrial dysfunction-related diseases, including PD.