%0 Journal Article
%A Rothemann, Robin Alexander
%A Pavlenko, Egor
%A Mondal, Mrityunjoy
%A Gerlich, Sarah
%A Grobushkin, Pavel
%A Mostert, Sebastian
%A Racho, Julia
%A Weiss, Konstantin
%A Stobbe, Dylan
%A Stillger, Katharina
%A Lapacz, Kim
%A Salscheider, Silja Lucia
%A Petrungaro, Carmelina
%A Ehninger, Dan
%A Nguyen, Thi Hoang Duong
%A Dengjel, Jörn
%A Neundorf, Ines
%A Bano, Daniele
%A Poepsel, Simon
%A Riemer, Jan
%T Interaction with AK2A links AIFM1 to cellular energy metabolism.
%J Molecular cell
%V 85
%N 13
%@ 1097-2765
%C [Cambridge, Mass.]
%I Cell Press
%M DZNE-2025-00773
%P 2550 - 2566.e6
%D 2025
%X 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.
%K AIFM1 (Other)
%K AK2 (Other)
%K ATP (Other)
%K ATP transport (Other)
%K MIA40/CHCHD4 (Other)
%K MICOS (Other)
%K metabolism (Other)
%K mitochondria (Other)
%F PUB:(DE-HGF)16
%9 Journal Article
%$ pmid:40578348
%R 10.1016/j.molcel.2025.05.036
%U https://pub.dzne.de/record/279442