Mitochondrial carrier homolog 1 (MTCH1)

Mitochondrial carrier homolog 1 (MTCH1) is a proapoptotic protein localized predominantly to the mitochondrial outer membrane, encoded by the MTCH1 gene (also known as SLC25A49 and Presenilin-associated protein)[1][4]. MTCH1 is structurally related to the mitochondrial carrier protein family, containing multiple isoforms generated by alternative splicing, all with apoptotic domains conferring a role in programmed cell death[4]. It induces apoptosis independently of canonical BCL-2 family regulators (such as BAX/BAK), likely through mitochondrial membrane depolarization, cytochrome c release, and subsequent caspase activation[1][4]. MTCH1 participates in key pathways regulating not only apoptosis but also ferroptosis, cell proliferation, and RNA splicing. It is implicated in cancer (notably as a potential oncogene and prognostic biomarker in hepatocellular carcinoma and a ferroptosis regulator in cervical cancer), as well as in neurodegenerative and neuroinflammatory diseases, possibly through its interactions with presenilin proteins. While MTCH1 remains an emerging therapeutic target, research suggests targeting its pathway could modulate tumor cell death resistance or sensitivity, as demonstrated in preclinical synergy with anticancer drugs like Sorafenib[2][3][4].

Other names

Presenilin-associated proteinPSAPSLC25A49CGI-64PIG60Cell proliferation-inducing protein 60Presenilin 1-associated protein

Induction of apoptosis via mitochondrial outer membrane permeabilization and cytochrome c release, independent of BAX/BAK[1][4]; Synergistic induction of ferroptosis with Sorafenib when MTCH1 expression is inhibited[2]; Stress-response apoptosis triggered via upregulation by early growth response protein 1 (EGR-1), especially after DNA damage[4]