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  • Title: Myosin VI-Dependent Actin Cages Encapsulate Parkin-Positive Damaged Mitochondria.
    Author: Kruppa AJ, Kishi-Itakura C, Masters TA, Rorbach JE, Grice GL, Kendrick-Jones J, Nathan JA, Minczuk M, Buss F.
    Journal: Dev Cell; 2018 Feb 26; 44(4):484-499.e6. PubMed ID: 29398621.
    Abstract:
    Mitochondrial quality control is essential to maintain cellular homeostasis and is achieved by removing damaged, ubiquitinated mitochondria via Parkin-mediated mitophagy. Here, we demonstrate that MYO6 (myosin VI), a unique myosin that moves toward the minus end of actin filaments, forms a complex with Parkin and is selectively recruited to damaged mitochondria via its ubiquitin-binding domain. This myosin motor initiates the assembly of F-actin cages to encapsulate damaged mitochondria by forming a physical barrier that prevents refusion with neighboring populations. Loss of MYO6 results in an accumulation of mitophagosomes and an increase in mitochondrial mass. In addition, we observe downstream mitochondrial dysfunction manifesting as reduced respiratory capacity and decreased ability to rely on oxidative phosphorylation for energy production. Our work uncovers a crucial step in mitochondrial quality control: the formation of MYO6-dependent actin cages that ensure isolation of damaged mitochondria from the network.
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