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Structure paper

タイトル	Interaction with AK2A links AIFM1 to cellular energy metabolism.
ジャーナル・号・ページ	Mol Cell, Vol. 85, Issue 13, Page 2550-22566.e6, Year 2025
掲載日	2025年7月3日
著者	Robin Alexander Rothemann / Egor Pavlenko / Mrityunjoy Mondal / Sarah Gerlich / Pavel Grobushkin / Sebastian Mostert / Julia Racho / Konstantin Weiss / Dylan Stobbe / Katharina Stillger / Kim Lapacz / Silja Lucia Salscheider / Carmelina Petrungaro / Dan Ehninger / Thi Hoang Duong Nguyen / Jörn Dengjel / Ines Neundorf / Daniele Bano / Simon Poepsel / Jan Riemer /
PubMed 要旨	Apoptosis-inducing factor 1 (AIFM1) is a flavoprotein essential for mitochondrial function and biogenesis. Its interaction with MIA40/CHCHD4, the central component of the mitochondrial disulfide ...Apoptosis-inducing factor 1 (AIFM1) is a flavoprotein essential for mitochondrial function and biogenesis. Its interaction with MIA40/CHCHD4, the central component of the mitochondrial disulfide relay, accounts for some, but not all, aspects of AIFM1 function. We provide a high-confidence AIFM1 interactome that elucidates functional partners within the mitochondrial intermembrane space. We found that AIFM1 binding to adenylate kinase 2 (AK2), an essential enzyme that maintains cellular adenine nucleotide pools, depends on the AK2 C-terminal domain. High-resolution cryoelectron microscopy (cryo-EM) and biochemical analyses showed that both MIA40 and AK2A bind the AIFM1 C-terminal β-sheet domain. Their binding enhances NADH oxidoreductase activity by locking an active dimer conformation and, in the case of MIA40, affecting the cofactor-binding site. The AIFM1-AK2A interaction is important during mitochondrial respiration because AIFM1 serves as a recruiting hub within the IMS, regulating mitochondrial bioenergetic output by creating hotspots of metabolic enzymes.
リンク	Mol Cell / PubMed:40578348
手法	EM (単粒子)
解像度	2.36 - 2.8 Å
構造データ	51514 9gqy EMDB-51514, PDB-9gqy: Interaction with AK2A links AIFM1 to cellular energy metabolism. The cryo-EM structure of dimeric AIFM1 without any binding partner. 手法: EM (単粒子) / 解像度: 2.8 Å 51515 9gqz EMDB-51515, PDB-9gqz: Interaction with AK2A links AIFM1 to cellular energy metabolism. The cryo-EM structure of dimeric AIFM1 engaged to MIA40. 手法: EM (単粒子) / 解像度: 2.36 Å 51516 9gr0 EMDB-51516, PDB-9gr0: Interaction with AK2A links AIFM1 to cellular energy metabolism. The cryo-EM structure of dimeric AIFM1 bound by AK2A. 手法: EM (単粒子) / 解像度: 2.61 Å
化合物	ChemComp-FAD: FLAVIN-ADENINE DINUCLEOTIDE / FAD / FADYM ChemComp-NAD: NICOTINAMIDE-ADENINE-DINUCLEOTIDE / NADYM ChemComp-HOH: WATER
由来	homo sapiens (ヒト)
キーワード	FLAVOPROTEIN / Complex / Homodimer / NADH / FAD / Reduced / Tetramer