Role of Mitochondria–ER Contact Sites in Mitophagy

Abstract

Mitochondria are often referred to as the “powerhouse” of the cell. However, this organelle has many more functions than simply satisfying the cells’ metabolic needs. Mitochondria are involved in calcium homeostasis and lipid metabolism, and they also regulate apoptotic processes. Many of these functions require contact with the ER, which is mediated by several tether proteins located on the respective organellar surfaces, enabling the formation of mitochondria–ER contact sites (MERCS). Upon damage, mitochondria produce reactive oxygen species (ROS) that can harm the surrounding cell. To circumvent toxicity and to maintain a functional pool of healthy organelles, damaged and excess mitochondria can be targeted for degradation via mitophagy, a form of selective autophagy. Defects in mitochondria–ER tethers and the accumulation of damaged mitochondria are found in several neurodegenerative diseases, including Parkinson’s disease and amyotrophic lateral sclerosis, which argues that the interplay between the two organelles is vital for neuronal health. This review provides an overview of the different mechanisms of mitochondrial quality control that are implicated with the different mitochondria–ER tether proteins, and also provides a novel perspective on how MERCS are involved in mediating mitophagy upon mitochondrial damage.

The Janus-faced functions of Apolipoproteins L in membrane dynamics

“…APOL1 co-localizes with PI4KB and APOL3 in ATG9A vesicles [16], known to traffic PI4KB from the Golgi to the mitochondrion for autophagy initiation, which occurs together with mitochondrion fission at MERCSs [44,70]. Moreover, APOL1 tightly associates with NM2A, the myosin known to be responsible for ATG9A vesicle trafficking [11,[71][72][73].…”