Journal Article

DZNE-2025-00773

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Interaction with AK2A links AIFM1 to cellular energy metabolism.

Rothemann, R. A. ; Pavlenko, E. ; Mondal, M.DZNE* ; Gerlich, S. ; Grobushkin, P. ; Mostert, S. ; Racho, J. ; Weiss, K. ; Stobbe, D. ; Stillger, K. ; Lapacz, K. ; Salscheider, S. L. ; Petrungaro, C. ; Ehninger, D.DZNE* ; Nguyen, T. H. D. ; Dengjel, J. ; Neundorf, I. ; Bano, D.DZNE* ; Poepsel, S. ; Riemer, J.

2025
Cell Press [Cambridge, Mass.]

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Please use a persistent id in citations: doi:10.1016/j.molcel.2025.05.036

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.

Keyword(s): AIFM1 ; AK2 ; ATP ; ATP transport ; MIA40/CHCHD4 ; MICOS ; metabolism ; mitochondria

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Contributing Institute(s):

1. Aging and Neurodegeneration (AG Bano)
2. Translational Biogerontology (AG Ehninger)

Research Program(s):

1. 351 - Brain Function (POF4-351) (POF4-351)
2. 352 - Disease Mechanisms (POF4-352) (POF4-352)

Appears in the scientific report 2025

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Database coverage:
; ; ; BIOSIS Previews ; Biological Abstracts ; Clarivate Analytics Master Journal List ; Current Contents - Life Sciences ; Ebsco Academic Search ; Essential Science Indicators ; IF >= 15 ; JCR ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

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