ATP-dependent RNA helicase SUPV3L1, mitochondrial (SUPV3L1) (SUPV3L1)

ATP-dependent RNA helicase SUPV3L1, mitochondrial (also known as SUV3), is a nuclear-encoded enzyme that localizes to the mitochondrial matrix and serves as a core component of the mitochondrial degradosome (UniProt Q8IYB8). In complex with the polynucleotide phosphorylase (PNPase), it forms the mtEXO complex, which is responsible for the surveillance and degradation of mitochondrial RNA (mtRNA), including non-coding transcripts and aberrantly processed molecules (PubMed: 19509288, 29967381). SUPV3L1 is essential for maintaining mitochondrial homeostasis and mitochondrial DNA (mtDNA) integrity (NIH, 2024-10-30). While biallelic mutations in the SUPV3L1 gene cause a rare neurodegenerative syndrome characterized by ataxia and spasticity, its overexpression has been identified as a therapeutic vulnerability in acute myeloid leukemia (AML) (ASH Publications, Blood 2023). Inhibition of SUPV3L1, often via mRNA-targeting approaches like siRNA, leads to the accumulation of mitochondrial double-stranded RNA (dsRNA), which triggers a 'viral mimicry' response and activates immune-mediated cell death in cancer cells (AACR, Cancer Res 2023). Currently, there are no approved drugs targeting SUPV3L1, but it remains an active area of research for cancer and mitochondrial-related pathologies.

Other names

SUV3hSuv3pSuppressor of var1 3-like protein 1SUV3L1Suppressor of variegation 3-like protein 1

Inhibition of mitochondrial RNA helicase activity or RNA interference-mediated degradation of SUPV3L1 mRNA, leading to the accumulation of mitochondrial double-stranded RNA and the induction of a viral mimicry response.