engleski

Regulation of mitophagy receptors by phosphorylation

Discoveries of autophagy receptors that recognize specific cellular cargo have opened a new chapter in the autophagy field. This selective removal of damaged organelles or protein aggregates is essential for proper cellular homeostasis and survival. Growing evidence of the function of particular autophagy receptors indicates that most of them are often working together in the same selective autophagy pathway, such as aggrephagy, xenophagy and mitophagy. In this part, we focused our research on receptors involved in mitophagy and their regulation. These receptors, such as Atg32, BNIP3 and BNIP3/NIX interact with Atg8/LC3/GABARAP family proteins in LIR-dependent manner and recruit autophagy machinery to damaged mitochondria. The lessons from xenophagy are directing future research towards better understanding of how mitophagy is activated and regulated. After all, this is not suprising, because there is well-accepted endosymbiotic theory that connects bacteria and mitochondria, where mitochondria are bacterial evolutionary descendants. Our results sugest that autophagic function of the receptor is regulated by phosphorylation but what is the trigger for the phosphorylation and activation of mitophagy is still obscure. Moreover, we showed cellular, biochemical and biophysical evidence that phosphorylation of LIR domain of Nix receptor is essential for mitophagy activation. Understanding of mitophagy regulation, and general autophagy, is the major challenge for researchers of our time and their answers will help us to better understand the role of receptors and autophagy in disease development such as Parkinson’s disease and a number of other diseases.

mitophagy; phosphorylation

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