TY  - JOUR
AU  - Rothemann, Robin Alexander
AU  - Pavlenko, Egor
AU  - Mondal, Mrityunjoy
AU  - Gerlich, Sarah
AU  - Grobushkin, Pavel
AU  - Mostert, Sebastian
AU  - Racho, Julia
AU  - Weiss, Konstantin
AU  - Stobbe, Dylan
AU  - Stillger, Katharina
AU  - Lapacz, Kim
AU  - Salscheider, Silja Lucia
AU  - Petrungaro, Carmelina
AU  - Ehninger, Dan
AU  - Nguyen, Thi Hoang Duong
AU  - Dengjel, Jörn
AU  - Neundorf, Ines
AU  - Bano, Daniele
AU  - Poepsel, Simon
AU  - Riemer, Jan
TI  - Interaction with AK2A links AIFM1 to cellular energy metabolism.
JO  - Molecular cell
VL  - 85
IS  - 13
SN  - 1097-2765
CY  - [Cambridge, Mass.]
PB  - Cell Press
M1  - DZNE-2025-00773
SP  - 2550 - 2566.e6
PY  - 2025
AB  - 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.
KW  - AIFM1 (Other)
KW  - AK2 (Other)
KW  - ATP (Other)
KW  - ATP transport (Other)
KW  - MIA40/CHCHD4 (Other)
KW  - MICOS (Other)
KW  - metabolism (Other)
KW  - mitochondria (Other)
LB  - PUB:(DE-HGF)16
C6  - pmid:40578348
DO  - DOI:10.1016/j.molcel.2025.05.036
UR  - https://pub.dzne.de/record/279442
ER  -