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000279442 1001_ $$aRothemann, Robin Alexander$$b0
000279442 245__ $$aInteraction with AK2A links AIFM1 to cellular energy metabolism.
000279442 260__ $$a[Cambridge, Mass.]$$bCell Press$$c2025
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000279442 520__ $$aApoptosis-inducing factor 1 (AIFM1) is a flavoprotein essential for mitochondrial function and biogenesis. Its interaction with MIA40/CHCHD4, the central component of the mitochondrial disulfide relay, accounts for some, but not all, aspects of AIFM1 function. We provide a high-confidence AIFM1 interactome that elucidates functional partners within the mitochondrial intermembrane space. We found that AIFM1 binding to adenylate kinase 2 (AK2), an essential enzyme that maintains cellular adenine nucleotide pools, depends on the AK2 C-terminal domain. High-resolution cryoelectron microscopy (cryo-EM) and biochemical analyses showed that both MIA40 and AK2A bind the AIFM1 C-terminal β-sheet domain. Their binding enhances NADH oxidoreductase activity by locking an active dimer conformation and, in the case of MIA40, affecting the cofactor-binding site. The AIFM1-AK2A interaction is important during mitochondrial respiration because AIFM1 serves as a recruiting hub within the IMS, regulating mitochondrial bioenergetic output by creating hotspots of metabolic enzymes.
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000279442 650_7 $$2Other$$aAIFM1
000279442 650_7 $$2Other$$aAK2
000279442 650_7 $$2Other$$aATP
000279442 650_7 $$2Other$$aATP transport
000279442 650_7 $$2Other$$aMIA40/CHCHD4
000279442 650_7 $$2Other$$aMICOS
000279442 650_7 $$2Other$$ametabolism
000279442 650_7 $$2Other$$amitochondria
000279442 7001_ $$aPavlenko, Egor$$b1
000279442 7001_ $$0P:(DE-2719)9001754$$aMondal, Mrityunjoy$$b2$$udzne
000279442 7001_ $$aGerlich, Sarah$$b3
000279442 7001_ $$aGrobushkin, Pavel$$b4
000279442 7001_ $$aMostert, Sebastian$$b5
000279442 7001_ $$aRacho, Julia$$b6
000279442 7001_ $$aWeiss, Konstantin$$b7
000279442 7001_ $$aStobbe, Dylan$$b8
000279442 7001_ $$aStillger, Katharina$$b9
000279442 7001_ $$aLapacz, Kim$$b10
000279442 7001_ $$aSalscheider, Silja Lucia$$b11
000279442 7001_ $$aPetrungaro, Carmelina$$b12
000279442 7001_ $$0P:(DE-2719)2289209$$aEhninger, Dan$$b13$$udzne
000279442 7001_ $$aNguyen, Thi Hoang Duong$$b14
000279442 7001_ $$aDengjel, Jörn$$b15
000279442 7001_ $$aNeundorf, Ines$$b16
000279442 7001_ $$0P:(DE-2719)2158358$$aBano, Daniele$$b17$$udzne
000279442 7001_ $$aPoepsel, Simon$$b18
000279442 7001_ $$aRiemer, Jan$$b19
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