Role of the c subunit of the F _O ATP synthase in mitochondrial permeability transition

Citations Over TimeTop 1% of 2013 papers

Abstract

The term "mitochondrial permeability transition" (MPT) refers to an abrupt increase in the permeability of the inner mitochondrial membrane to low molecular weight solutes. Due to osmotic forces, MPT is paralleled by a massive influx of water into the mitochondrial matrix, eventually leading to the structural collapse of the organelle. Thus, MPT can initiate mitochondrial outer membrane permeabilization (MOMP), promoting the activation of the apoptotic caspase cascade as well as of caspase-independent cell death mechanisms. MPT appears to be mediated by the opening of the so-called "permeability transition pore complex" (PTPC), a poorly characterized and versatile supramolecular entity assembled at the junctions between the inner and outer mitochondrial membranes. In spite of considerable experimental efforts, the precise molecular composition of the PTPC remains obscure and only one of its constituents, cyclophilin D (CYPD), has been ascribed with a crucial role in the regulation of cell death. Conversely, the results of genetic experiments indicate that other major components of the PTPC, such as voltage-dependent anion channel (VDAC) and adenine nucleotide translocase (ANT), are dispensable for MPT-driven MOMP. Here, we demonstrate that the c subunit of the FO ATP synthase is required for MPT, mitochondrial fragmentation and cell death as induced by cytosolic calcium overload and oxidative stress in both glycolytic and respiratory cell models. Our results strongly suggest that, similar to CYPD, the c subunit of the FO ATP synthase constitutes a critical component of the PTPC.

Related Papers

• → The role of the Bcl-2 family in the regulation of outer mitochondrial membrane permeability(2000)515 cited
• → Outer mitochondrial membrane permeability can regulate coupled respiration and cell survival(2000)437 cited
• → Targeting of proteins to mitochondria(2000)128 cited
• → Dual Role of Mitochondrial Porin in Metabolite Transport across the Outer Membrane and Protein Transfer to the Inner Membrane(2019)73 cited
• CHARACTERIZATION OF MITOCHONDRIAL MEMBRANE PROTEINS AS NOVEL COMPONENTS IN MITOCHONDRIAL DYNAMICS(2014)