RESUMO
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.
Assuntos
Ciclofilinas/metabolismo , Metaloendopeptidases/genética , Metaloendopeptidases/metabolismo , Mitocôndrias/metabolismo , Canal de Ânion 1 Dependente de Voltagem/metabolismo , ATPases Associadas a Diversas Atividades Celulares , Sítios de Ligação , Cálcio/metabolismo , Morte Celular , Ciclofilinas/química , Células HEK293 , Células HeLa , Humanos , Potencial da Membrana Mitocondrial , Metaloendopeptidases/química , Membranas Mitocondriais/metabolismo , Interferência de RNA , Espécies Reativas de Oxigênio/metabolismoRESUMO
We discuss a rare case of acute Type A thoracic aortic dissection (TAAD) following endovascular aneurysm repair (EVAR) of a common iliac artery aneurysm, which likely resulted from complications due to aberrant anatomy. Valve replacement, ascending aortic arch graft, and entry tear suture repair were necessary to contain the TAAD. Postoperative computed tomography with angiography (CTA) demonstrated stable disease, and the patient remained asymptomatic. Open and endovascular repair of the descending abdominal aorta was avoided. Few cases in the literature report TAAD following EVAR. Detection and repair of the entry site was crucial for containing the TAAD.