Selective autophagy of mitochondria on a ubiquitin-endoplasmic reticulum platform

Maria Zachari, Sigurdur R. Gudmundsson, Ziyue Li, Maria Manifava, Ronak Shah, Matthew Smith, James Stronge, Eleftherios Karanasios, Caterina Piunti, Chieko Kishi-Itakura, Helena Vihinen, Eija Jokitalo, Jun-Lin Guan, Folma Buss, Andrew M. Smith, Simon A. Walker, Eeva-Liisa Eskelinen, Nicholas T. Ktistakis

Forskningsoutput: TidskriftsbidragArtikelVetenskapligPeer review

Sammanfattning

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.
Originalspråkengelska
TidskriftDevelopmental Cell
Volym50
Utgåva5
Sidor (från-till)627-+
Antal sidor22
ISSN1534-5807
DOI
StatusPublicerad - 9 sep 2019
MoE-publikationstypA1 Tidskriftsartikel-refererad

Vetenskapsgrenar

  • 1182 Biokemi, cell- och molekylärbiologi

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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, 50(5), 627-+. https://doi.org/10.1016/j.devcel.2019.06.016