7YDO

Crystal structure of Atg44

Summary for 7YDO

• Entry DOI: 10.2210/pdb7ydo/pdb
• Descriptor: Uncharacterized protein C26A3.14c, 1,2-Distearoyl-sn-glycerophosphoethanolamine (3 entities in total)
• Functional Keywords: autophagy, mitophagy, lipid binding protein
• Biological source: Schizosaccharomyces pombe (strain 972 / ATCC 24843) (fission yeast)
• Total number of polymer chains: 4
• Total formula weight: 38712.34

Authors

Maruyama, T.,Noda, N.N. (deposition date: 2022-07-04, release date: 2023-05-17, Last modification date: 2024-05-29)

Primary citation

Fukuda, T.,Furukawa, K.,Maruyama, T.,Yamashita, S.I.,Noshiro, D.,Song, C.,Ogasawara, Y.,Okuyama, K.,Alam, J.M.,Hayatsu, M.,Saigusa, T.,Inoue, K.,Ikeda, K.,Takai, A.,Chen, L.,Lahiri, V.,Okada, Y.,Shibata, S.,Murata, K.,Klionsky, D.J.,Noda, N.N.,Kanki, T.
The mitochondrial intermembrane space protein mitofissin drives mitochondrial fission required for mitophagy.
Mol.Cell, 83:2045-2058.e9, 2023

PubMed Abstract: Mitophagy plays an important role in mitochondrial homeostasis by selective degradation of mitochondria. During mitophagy, mitochondria should be fragmented to allow engulfment within autophagosomes, whose capacity is exceeded by the typical mitochondria mass. However, the known mitochondrial fission factors, dynamin-related proteins Dnm1 in yeasts and DNM1L/Drp1 in mammals, are dispensable for mitophagy. Here, we identify Atg44 as a mitochondrial fission factor that is essential for mitophagy in yeasts, and we therefore term Atg44 and its orthologous proteins mitofissin. In mitofissin-deficient cells, a part of the mitochondria is recognized by the mitophagy machinery as cargo but cannot be enwrapped by the autophagosome precursor, the phagophore, due to a lack of mitochondrial fission. Furthermore, we show that mitofissin directly binds to lipid membranes and brings about lipid membrane fragility to facilitate membrane fission. Taken together, we propose that mitofissin acts directly on lipid membranes to drive mitochondrial fission required for mitophagy.

PubMed: 37192628
DOI: 10.1016/j.molcel.2023.04.022

Experimental method

X-RAY DIFFRACTION (1.58 Å)