SPG7 Is an Essential and Conserved Component of the Mitochondrial Permeability Transition Pore.
Mol Cell
; 60(1): 47-62, 2015 Oct 01.
Article
en En
| MEDLINE
| ID: mdl-26387735
ABSTRACT
Mitochondrial permeability transition is a phenomenon in which the mitochondrial permeability transition pore (PTP) abruptly opens, resulting in mitochondrial membrane potential (ΔΨm) dissipation, loss of ATP production, and cell death. Several genetic candidates have been proposed to form the PTP complex, however, the core component is unknown. We identified a necessary and conserved role for spastic paraplegia 7 (SPG7) in Ca(2+)- and ROS-induced PTP opening using RNAi-based screening. Loss of SPG7 resulted in higher mitochondrial Ca(2+) retention, similar to cyclophilin D (CypD, PPIF) knockdown with sustained ΔΨm during both Ca(2+) and ROS stress. Biochemical analyses revealed that the PTP is a heterooligomeric complex composed of VDAC, SPG7, and CypD. Silencing or disruption of SPG7-CypD binding prevented Ca(2+)- and ROS-induced ΔΨm depolarization and cell death. This study identifies an ubiquitously expressed IMM integral protein, SPG7, as a core component of the PTP at the OMM and IMM contact site.
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Metaloendopeptidasas
/
Ciclofilinas
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Canal Aniónico 1 Dependiente del Voltaje
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Mitocondrias
Tipo de estudio:
Prognostic_studies
Límite:
Humans
Idioma:
En
Año:
2015
Tipo del documento:
Article