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@ARTICLE{Rothemann:279442,
author = {Rothemann, Robin Alexander and Pavlenko, Egor and Mondal,
Mrityunjoy and Gerlich, Sarah and Grobushkin, Pavel and
Mostert, Sebastian and Racho, Julia and Weiss, Konstantin
and Stobbe, Dylan and Stillger, Katharina and Lapacz, Kim
and Salscheider, Silja Lucia and Petrungaro, Carmelina and
Ehninger, Dan and Nguyen, Thi Hoang Duong and Dengjel, Jörn
and Neundorf, Ines and Bano, Daniele and Poepsel, Simon and
Riemer, Jan},
title = {{I}nteraction with {AK}2{A} links {AIFM}1 to cellular
energy metabolism.},
journal = {Molecular cell},
volume = {85},
number = {13},
issn = {1097-2765},
address = {[Cambridge, Mass.]},
publisher = {Cell Press},
reportid = {DZNE-2025-00773},
pages = {2550 - 2566.e6},
year = {2025},
abstract = {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.},
keywords = {AIFM1 (Other) / AK2 (Other) / ATP (Other) / ATP transport
(Other) / MIA40/CHCHD4 (Other) / MICOS (Other) / metabolism
(Other) / mitochondria (Other)},
cin = {AG Bano / AG Ehninger},
ddc = {610},
cid = {I:(DE-2719)1013003 / I:(DE-2719)1013005},
pnm = {351 - Brain Function (POF4-351) / 352 - Disease Mechanisms
(POF4-352)},
pid = {G:(DE-HGF)POF4-351 / G:(DE-HGF)POF4-352},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:40578348},
doi = {10.1016/j.molcel.2025.05.036},
url = {https://pub.dzne.de/record/279442},
}