Lipid droplet turnover at the lysosome inhibits growth of hepatocellular carcinoma in a BNIP3-dependent manner.
Lipid droplet turnover at the lysosome inhibits growth of hepatocellular carcinoma in a BNIP3-dependent manner.
复制标题
溶酶体脂滴转换以bnip3依赖的方式抑制肝细胞癌的生长。
DOI：
10.1126/sciadv.abo2510
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发表时间：
2022-10-14
期刊：
影响因子：
13.6
通讯作者：
Macleod, Kay F.
中科院分区：
文献类型：
--
作者：
Berardi, Damian E.;Bock-Hughes, Althea;Terry, Alexander R.;Drake, Lauren E.;Bozek, Grazyna;Macleod, Kay F.
肝脂肪变性是肝细胞癌（HCC）的主要病因，但引起脂质积聚导致HCC的因素尚不清楚。我们确定BNIP 3（线粒体货物受体）作为HCC抑制因子，可减轻脂质积聚以减弱肿瘤细胞生长。在HCC小鼠模型中，Bnip 3的靶向缺失降低了肿瘤潜伏期并增加了肿瘤负荷。这与疾病早期bnip 3 −/− HCC中脂质增加有关，而脂质直到野生型小鼠肿瘤发生后期才积累，因为Bnip 3表达减弱。与高表达BNIP 3的HCC相比，人HCC中BNIP 3低表达同样与脂质含量增加和更差的预后相关。BNIP 3通过以依赖于BNIP 3结合LC 3的方式促进溶酶体处的脂滴周转来抑制HCC细胞生长。我们把这个过程称为“线粒体吞噬”，因为它涉及到与线粒体协调的脂滴自噬降解。在“线粒体吞噬”中线粒体的脂滴周转需要BNIP 3，并且在肝细胞癌中被破坏。
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 Bnip3 decreased tumor latency and increased tumor burden in a mouse model of HCC. This was associated with increased lipid in bnip3−/− HCC at early stages of disease, while lipid did not accumulate until later in tumorigenesis in wild-type mice, as Bnip3 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. Lipid droplet turnover with mitochondria in “mitolipophagy” requires BNIP3 and is disrupted in hepatocellular carcinoma.
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影响因子：
7.3
作者：
Gao J;Aksoy BA;Dogrusoz U;Dresdner G;Gross B;Sumer SO;Sun Y;Jacobsen A;Sinha R;Larsson E;Cerami E;Sander C;Schultz N
通讯作者：
Schultz N
影响因子：
21.3
作者：
通讯作者：
--
影响因子：
16
作者：
Kashatus, Jennifer A.;Nascimento, Aldo;Myers, Lindsey J.;Sher, Annie;Byrne, Frances L.;Hoehn, Kyle L.;Counter, Christopher M.;Kashatus, David F.
通讯作者：
Kashatus, David F.
DOI：
10.1038/s41575-020-00381-6
发表时间：
2021-04
期刊：
Nature reviews. Gastroenterology & hepatology
影响因子：
--
作者：
Huang DQ;El-Serag HB;Loomba R
通讯作者：
Loomba R
影响因子：
158.5
作者：
Calle, EE;Rodriguez, C;Thun, MJ
通讯作者：
Thun, MJ