NADH:ubiquinone oxidoreductase subunit A13 (NDUFA13) (NDUFA13)

NADH:ubiquinone oxidoreductase subunit A13 (NDUFA13), widely known as GRIM-19, is a dual-function protein essential for both mitochondrial bioenergetics and the regulation of cell survival [1.2.2, 1.3.4]. As a core accessory subunit of the mitochondrial respiratory chain Complex I, it is indispensable for the assembly and electron transfer activity of the complex, which drives ATP production [1.1.4, 1.3.5]. Independently of its mitochondrial role, NDUFA13 functions as a non-canonical tumor suppressor by physically interacting with the STAT3 transcription factor, effectively blocking its nuclear translocation and subsequent activation of pro-survival genes [1.3.1, 1.4.1]. The gene was first discovered as a necessary component for the synergistic cell death induced by interferon-beta and retinoic acid in cancer cells [1.2.2, 1.3.4]. Clinical studies have shown that NDUFA13 expression is frequently lost or significantly reduced in numerous cancers, such as renal cell carcinoma and gastric cancer, correlating with poor prognosis and metastasis [1.2.5, 1.3.1]. Pharmacologically, NDUFA13 is involved in the mechanism of action of metformin, which targets Complex I, and its presence modulates the efficacy of microtubule-stabilizing agents like paclitaxel [1.1.1, 1.1.4]. Therapeutic research is currently investigating the restoration of NDUFA13 levels as a means to suppress STAT3-driven oncogenesis and treat inflammatory conditions [1.3.1, 1.4.2].

Other names

GRIM-19GRIM19Gene associated with retinoid-interferon-induced mortality 19Gene associated with retinoic-interferon-induced mortality 19CGI-39CDA016B16.6Cell death-regulatory protein GRIM-19

Inhibition of mitochondrial Complex I; Inhibition of STAT3 nuclear translocation and transcriptional activity; Induction of apoptosis via the IFN-beta/RA pathway [1.1.4, 1.3.1, 1.4.1]