Mitophagy programs: mechanisms and physiological implications of mitochondrial targeting by autophagy

作者：Hamacher Brady Anne; Brady Nathan Ryan

来源：Cellular and Molecular Life Sciences, 2016, 73(4): 775-795.

DOI：10.1007/s00018-015-2087-8

• Bnip3
• FUNDC1
• LC3-interacting region (LIR)
• Macroautophagy
• Mitophagy
• Nix
• Parkin E3 ligase
• Ubiquitin

Mitochondria are an essential source of ATP for cellular function, but when damaged, mitochondria generate a plethora of stress signals, which lead to cellular dysfunction and eventually programmed cell death. Thus, a major component of maintaining cellular homeostasis is the recognition and removal of dysfunctional mitochondria through autophagy-mediated degradation, i.e., mitophagy. Mitophagy further constitutes a developmental program, and undergoes a high degree of crosstalk with apoptosis. Reduced mitochondrial quality control is linked to disease pathogenesis, suggesting the importance of process elucidation as a clinical target. Recent work has revealed multiple mitophagy programs that operate independently or undergo crosstalk, and require modulated autophagy receptor activities at outer membranes of mitochondria. Here, we review these mitophagy programs, focusing on pathway mechanisms which recognize and target mitochondria for sequestration by autophagosomes, as well as mechanisms controlling pathway activities. Furthermore, we provide an introduction to the currently available methods for detecting mitophagy.

• 出版日期2016-2