9FL7

Cryo-EM structure of human AK2 bound to reduced human AIFM1 (residues 102-613), class 3

9FL7 の概要

• エントリーDOI: 10.2210/pdb9fl7/pdb
• EMDBエントリー: 50532
• 分子名称: Apoptosis-inducing factor 1, mitochondrial, Adenylate kinase 2, mitochondrial, NICOTINAMIDE-ADENINE-DINUCLEOTIDE, ... (4 entities in total)
• 機能のキーワード: mitochondria, mitochondrial intermembrane space, ims, mitochondrial inner membrane, im, apoptosis-inducing factor 1, adenylate kinase, flavoprotein
• 由来する生物種: Homo sapiens (human); 詳細
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 143077.75

構造登録者

Lauer, S.M.,Spahn, C.M.T.,Schwefel, D. (登録日: 2024-06-04, 公開日: 2025-05-14, 最終更新日: 2025-07-16)

主引用文献

Schildhauer, F.,Ryl, P.S.J.,Lauer, S.M.,Lenz, S.,Barlas, A.B.,Ouzounidis, V.R.,Jeffrey, K.,Marcu, D.C.,O'Reilly, F.J.,Graziadei, A.,Stuiver, M.,Schmidt, K.,Ewers, H.,Spahn, C.M.T.,Karaca, E.,Busch, K.E.,Cheerambathur, D.,Schwefel, D.,Rappsilber, J.
An NADH-controlled gatekeeper of ATP synthase.
Mol.Cell, 85:2567-2580.e12, 2025

PubMed Abstract: ATP fuels crucial cellular processes and is obtained mostly by oxidative phosphorylation (OXPHOS) at the inner mitochondrial membrane. While significant progress has been made in mechanistic understanding of ATP production, critical aspects surrounding its substrate supply logistics are poorly understood. We identify an interaction between mitochondrial apoptosis-inducing factor 1 (AIFM1) and adenylate kinase 2 (AK2) as gatekeeper of ATP synthase. This interaction is NADH dependent and influenced by glycolysis, linking it to the cell's metabolic state. Genetic interference with AIFM1/AK2 association impedes the ability of Caenorhabditis elegans animals to handle altered metabolic rates and nutrient availability. Together, the results imply AIFM1 as a cellular NADH sensor, placing AK2 next to the OXPHOS complexes for local ADP regeneration as the substrate for ATP synthesis. This metabolic signal relay balances ATP synthase substrate supply against ATP conservation, enabling cells to adapt to fluctuating energy availability, with possible implications for AIFM1-related mitochondrial diseases.

PubMed: 40578349
DOI: 10.1016/j.molcel.2025.06.007

実験手法

ELECTRON MICROSCOPY (4.3 Å)