Abstract
Mitochondria are highly dynamic organelles, which can form a network in cells through fusion, fission, and tubulation. Its morphology is closely related to the function of mitochondria. The damaged mitochondria can be removed by mitophagy. However, the relationship between mitochondrial morphology and non-selective autophagy is not fully understood. We found that mitochondrial fusion machinery, not fission or tubulation machinery, is essential for energy deprivation-induced autophagy. In response to glucose starvation, deletion of mitochondrial fusion proteins severely impaired the association of Atg1/ULK1 with Atg13, and then affected the recruitment of Atg1 and other autophagic proteins to PAS (phagophore assembly site). Furthermore, the deletion of fusion proteins blocks mitochondrial respiration, the binding of Snf1-Mec1, the phosphorylation of Mec1 by Snf1, and the dissociation of Mec1 from mitochondria under prolonged starvation. We propose that mitochondrial fusion machinery regulates energy deprivation-induced autophagy through maintaining mitochondrial respiration.
Highlights
Autophagy is a highly conserved material degradation pathway from yeast to human
Under either nitrogen starvation or glucose starvation, there is no significant difference in the cleavage of GFP-Atg8 compared with wild type, indicating that mitochondrial fission machinery is not involved in autophagy induced by nitrogen starvation and glucose starvation
These results indicated that mitochondrial fusion machinery is essential for glucose starvation-induced autophagy
Summary
Autophagy is a highly conserved material degradation pathway from yeast to human. It can degrade long-lived proteins, damaged organelles, aggregates, lipid droplets, and RNA, etc (Ohsumi, 2014). In the process of autophagy, a double-layer membrane structure envelops these substances to form autophagosome. These substances are degraded by acid hydrolase in lysosomes/vacuoles (Shibutani and Yoshimori, 2014). Based on different degradation substrates, autophagy can be classified into non-selective autophagy and selective autophagy. Non-selective autophagy is usually called as autophagy/macroautophagy, which has no selectivity for degradation substrates. Selective autophagy is mediated by specific autophagy receptors.
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