biostudies-literatureMussulini BHMEuropean Molecular Biology OrganizationFundacja na rzecz Nauki PolskiejFundacja na rzecz Nauki Polskiej (FNP)Narodowe Centrum NaukiEuropean Molecular Biology Organization (EMBO)Narodowe Centrum Nauki (NCN)1835-1862https://www.ebi.ac.uk/biostudies/studies/S-EPMC11976965biostudies-literatureUnknown26(7)Mitochondria harbor respiratory complexes that perform oxidative phosphorylation. Complex I is the first enzyme of the respiratory chain that oxidizes NADH. A dysfunction in complex I can result in higher cellular levels of NADH, which in turn strengthens the interaction between apoptosis-inducing factor 1 (AIFM1) and Mitochondrial intermembrane space import and assembly protein 40 (MIA40) in the mitochondrial intermembrane space. We investigated whether MIA40 modulates the activity of AIFM1 upon increased NADH/NAD+ balance. We found that in model cells characterized by an increase in NADH the AIFM1-MIA40 interaction is strengthened and these cells demonstrate resistance to AIFM1-induced cell death. Either silencing of MIA40, rescue of complex I, or depletion of NADH through the expressionEMBO reportsMIA40 suppresses cell death induced by apoptosis-inducing factor 1.PMC11976965ALTF 388-20232019/35/B/NZ3/040952019/33/B/NZ5/007802019/35/B/NZ3/04066MAB/2017/2Ayyamperumal SWasilewski MChacinska AWnorowski ADraczkowski PBorrero-Landazabal MAMussulini BHMMaruszczak KKfalseMIA40 suppresses cell death induced by apoptosis-inducing factor 1.Mitochondria harbor respiratory complexes that perform oxidative phosphorylation. Complex I is the first enzyme of the respiratory chain that oxidizes NADH. A dysfunction in complex I can result in higher cellular levels of NADH, which in turn strengthens the interaction between apoptosis-inducing factor 1 (AIFM1) and Mitochondrial intermembrane space import and assembly protein 40 (MIA40) in the mitochondrial intermembrane space. We investigated whether MIA40 modulates the activity of AIFM1 upon increased NADH/NAD+ balance. We found that in model cells characterized by an increase in NADH the AIFM1-MIA40 interaction is strengthened and these cells demonstrate resistance to AIFM1-induced cell death. Either silencing of MIA40, rescue of complex I, or depletion of NADH through the expression2025-01-01T00:00:00Z2025 Apr2026-07-15T11:01:47.529Z2026-07-03T03:16:14.689ZS-EPMC119769654005546510.1038/s44319-025-00406-8