The protein encoded by this gene belongs to a class of eukaryotic CX(9)C proteins characterized by four cysteine residues spaced ten amino acids apart from one another. These residues form disulfide linkages that define a CHCH fold. In response to stress, the protein translocates from the mitochondrial intermembrane space to the nucleus where it binds to a highly conserved 13 nucleotide oxygen responsive element in the promoter of cytochrome oxidase 4I2, a subunit of the terminal enzyme of the electron transport chain.
In concert with recombination signal sequence-binding protein J, binding of this protein activates the oxygen responsive element at four percent oxygen. In addition, it has been shown that this protein is a negative regulator of mitochondria-mediated apoptosis. In response to apoptotic stimuli, mitochondrial levels of this protein decrease, allowing BCL2-associated X protein to oligomerize and activate the Caspase Cascade. Pseudogenes of this gene are found on multiple chromosomes. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Feb 2016].
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Ogaki K, Koga S, Heckman MG, Fiesel FC, Ando M, Labbé C, Lorenzo-Betancor O, Moussaud-Lamodière EL, Soto-Ortolaza AI, Walton RL, Strongosky AJ, Uitti RJ, McCarthy A, Lynch T, Siuda J, Opala G, Rudzinska M, Krygowska-Wajs A, Barcikowska M, Czyzewski K, Puschmann A, Nishioka K, Funayama M, Hattori N, Parisi JE, Petersen RC, Graff-Radford NR, Boeve BF, Springer W, Wszolek ZK, Dickson DW, Ross OA (December 2015). "Mitochondrial targeting sequence variants of the CHCHD2 gene are a risk for Lewy body disorders". Neurology. 85 (23): 2016–25. doi:10.1212/WNL.0000000000002170. PMC4676755. PMID26561290.
