Mitochondrial protein phosphatase 2C (PP2Cm)

Mitochondrial protein phosphatase 2C (PP2Cm) is a serine/threonine phosphatase located in the mitochondrial matrix, highly conserved among vertebrates, and especially expressed in the heart and brain. It regulates the mitochondrial permeability transition pore (mPTP), a non-selective channel in the inner mitochondrial membrane that opens in response to calcium overload, oxidative stress, or other signals, facilitating cell death or survival. PP2Cm deficiency increases sensitivity to calcium-induced mPTP opening, leads to cell death, and is required for normal cardiac and neural development[5][7]. While PP2Cm is a novel essential regulator, the pore-forming subunits of mPTP remain controversial, with candidates including the adenine nucleotide translocase, phosphate carrier, F-ATP synthase, and Cyclophilin D[1][4][6].

Other names

Protein phosphatase 2C, mitochondrial (PP2Cm)PP2C-type mitochondrial protein phosphatase(Alternative novel proteins involved in mPTP regulation include ATAD3A[3], Cyclophilin D[4], and others, but PP2Cm fits the description of a "novel" essential regulator published in key studies.)

For Cyclosporin A: inhibition of Cyclophilin D, preventing conformational changes required for mPTP opening[4][3] - For hypothetical PP2Cm-targeting drugs: modulation of protein phosphorylation status to regulate mPTP sensitivity to calcium overload[5][7]