MFSD7C switches mitochondrial ATP synthesis to thermogenesis in response to heme.
Nat Commun
; 11(1): 4837, 2020 09 24.
Article
en En
| MEDLINE
| ID: mdl-32973183
ABSTRACT
ATP synthesis and thermogenesis are two critical outputs of mitochondrial respiration. How these outputs are regulated to balance the cellular requirement for energy and heat is largely unknown. Here we show that major facilitator superfamily domain containing 7C (MFSD7C) uncouples mitochondrial respiration to switch ATP synthesis to thermogenesis in response to heme. When heme levels are low, MSFD7C promotes ATP synthesis by interacting with components of the electron transport chain (ETC) complexes III, IV, and V, and destabilizing sarcoendoplasmic reticulum Ca2+-ATPase 2b (SERCA2b). Upon heme binding to the N-terminal domain, MFSD7C dissociates from ETC components and SERCA2b, resulting in SERCA2b stabilization and thermogenesis. The heme-regulated switch between ATP synthesis and thermogenesis enables cells to match outputs of mitochondrial respiration to their metabolic state and nutrient supply, and represents a cell intrinsic mechanism to regulate mitochondrial energy metabolism.
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Proteínas de Transporte de Membrana
/
Receptores Virales
/
Adenosina Trifosfato
/
Termogénesis
/
Hemo
/
Mitocondrias
Límite:
Animals
/
Humans
Idioma:
En
Revista:
Nat Commun
Asunto de la revista:
BIOLOGIA
/
CIENCIA
Año:
2020
Tipo del documento:
Article
País de afiliación:
Estados Unidos