Phosphorylation Events in Selective Mitophagy: Possible Biochemical Markers?
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AUTOPHAGY (CT CHU, SECTION EDITOR)
Phosphorylation Events in Selective Mitophagy: Possible Biochemical Markers? Weilin Zhang • Hao Wu • Lei Liu • Yushan Zhu Quan Chen
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Published online: 9 November 2013 Springer Science+Business Media New York 2013
Abstract Mitophagy, or mitochondrial autophagy, plays an important role in mitochondrial quality control for the selective removal of damaged or unwanted mitochondria. Several molecules, including Parkin, p62 and the mitophagy receptors ATG32, NIX/BNIP3 and FUNDC1, were found to participate selective mitophagy. One critical question is how mitochondrial damage-related signals are sensed and transduced to activate mitophagy. It is emerging that mitophagy is highly regulated by reversible protein phosphorylation. Several kinases were found to be involved in selective mitophagy. Pink1 can phosphorylate Parkin to facilitate the subsequent activation of mitophagy. Casein kinase 2 was found to phosphorylate ATG32 in yeast to promote mitophagy. In contrast, Src kinase phosphorylates FUNDC1 to prevent its interaction with LC3, and the dephosphorylation of FUNDC1 is correlated with the activation of mitophagy in mammalian cells in response to hypoxia. Here, we focus on recent advances in our understanding of the signaling events that activate mitophagy and the implications of these events in diseases. We further suggest the possibility that the phosphorylation status of mitophagy receptors may serve as a biochemical marker of this critical process.
W. Zhang H. Wu L. Liu Q. Chen (&) The State Key Laboratory of Biomembrane and Membrane Biotechnology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China e-mail: [email protected] Y. Zhu Q. Chen Tianjin Key Laboratory of Protein Science, College of Life Sciences, Nankai University, Tianjin 300071, China
Keywords Mitophagy Mitochondrial autophagy Kinases Phosphorylation Biochemical markers Pathobiology
Introduction Mitochondria play pivotal roles in the production of cellular ATP and metabolites required for normal cellular activities essential for cell survival and programmed cell death (both apoptosis and programmed necrosis) [1–4]. Moreover, mitochondria produce superoxide as an inevitable byproduct during electron transfer along the mitochondrial respiratory chain [5–8]. In addition, mitochondria are the center for iron metabolism for the synthesis of both the heme and iron–sulfur cluster, which are two classes of iron-containing molecules [7, 9]. To fulfill such diverse or even opposing functions, mitochondrial quality must be tightly monitored to avoid harmful effects from mitochondria and to maintain the health of the cell [10–14]. The accumulation of dysfunctional mitochondria is the characteristic of different types of diseases, including heart failure, Alzheimer’s disease, Parkinson’s disease and cancers [15–18]. One of the reasons could be defective mitochondrial quality control. A better understanding of the molecular mechanism of mitochondrial quality control holds promise in the
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