Selective autophagy of mitochondria on a ubiquitin-endoplasmic reticulum platform

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Zachari , M , Gudmundsson , S R , Li , Z , Manifava , M , Shah , R , Smith , M , Stronge , J , Karanasios , E , Piunti , C , Kishi-Itakura , C , Vihinen , H , Jokitalo , E , Guan , J-L , Buss , F , Smith , A M , Walker , S A , Eskelinen , E-L & Ktistakis , N T 2019 , ' Selective autophagy of mitochondria on a ubiquitin-endoplasmic reticulum platform ' , Developmental Cell , vol. 50 , no. 5 , pp. 627-+ . https://doi.org/10.1016/j.devcel.2019.06.016

Title: Selective autophagy of mitochondria on a ubiquitin-endoplasmic reticulum platform
Author: Zachari, Maria; Gudmundsson, Sigurdur R.; Li, Ziyue; Manifava, Maria; Shah, Ronak; Smith, Matthew; Stronge, James; Karanasios, Eleftherios; Piunti, Caterina; Kishi-Itakura, Chieko; Vihinen, Helena; Jokitalo, Eija; Guan, Jun-Lin; Buss, Folma; Smith, Andrew M.; Walker, Simon A.; Eskelinen, Eeva-Liisa; Ktistakis, Nicholas T.
Contributor: University of Helsinki, Autophagy
University of Helsinki, Institute of Biotechnology
University of Helsinki, University Management
University of Helsinki, Molecular and Integrative Biosciences Research Programme
Date: 2019-09-09
Language: eng
Number of pages: 22
Belongs to series: Developmental Cell
ISSN: 1534-5807
URI: http://hdl.handle.net/10138/305804
Abstract: The dynamics and co-ordination between autophagy machinery and selective receptors during mitophagy are unknown. Also unknown is whether mitophagy depends on pre-existing membranes, or is triggered on the surface of damaged mitochondria. Using a ubiquitin-dependent mitophagy inducer, the lactone ivermectin, we have combined genetic and imaging experiments to address these questions. Ubiquitination of mitochondrial fragments is required earliest followed by autophosphorylation of TBK1. Next, early essential autophagy proteins FIP200 and ATG13 act at different steps whereas ULK1/2 are dispensable. Receptors act temporally and mechanistically upstream of ATG13 but downstream of FIP200. The VPS34 complex functions at the omegasome step. ATG13 and optineurin target mitochondria in a discontinuous oscillatory way suggesting multiple initiation events. Targeted ubiquitinated mitochondrial are cradled by endoplasmic reticulum strands even without functional autophagy machinery and mitophagy adaptors. We propose that damaged mitochondria are ubiquitinated and dynamically encased in ER strands providing platforms for formation of the mitophagosomes.
Subject: 1182 Biochemistry, cell and molecular biology
autophagy
mitophagy
ivermectin
ubiquitin
endoplasmic reticulum
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