Lipid droplet turnover at the lysosome inhibits growth of hepatocellular carcinoma in a BNIP3-dependent manner.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 36223464.
- Also identified by DOI 10.1126/sciadv.abo2510 and PMC identifier 9555787.
- Licence recorded as CC BY-NC.
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Abstract
Hepatic steatosis is a major etiological factor in hepatocellular carcinoma (HCC), but factors causing lipid accumulation leading to HCC are not understood. We identify BNIP3 (a mitochondrial cargo receptor) as an HCC suppressor that mitigates against lipid accumulation to attenuate tumor cell growth. Targeted deletion of <i>Bnip3</i> decreased tumor latency and increased tumor burden in a mouse model of HCC. This was associated with increased lipid in <i>bnip3</i><sup>-/-</sup> HCC at early stages of disease, while lipid did not accumulate until later in tumorigenesis in wild-type mice, as <i>Bnip3</i> expression was attenuated. Low BNIP3 expression in human HCC similarly correlated with increased lipid content and worse prognosis than HCC expressing high BNIP3. BNIP3 suppressed HCC cell growth by promoting lipid droplet turnover at the lysosome in a manner dependent on BNIP3 binding LC3. We have termed this process "mitolipophagy" because it involves the coordinated autophagic degradation of lipid droplets with mitochondria.