CPT1a regulates the delivery of extracellular fatty acids for cardiolipin turnover in prostate cancer cells.
Santiappillai, N. T.; Hakeem-Sanni, M. F.; Withy, A.; Butler, L. M.; Quek, L.-E.; Hoy, A. J.
Show abstract
Mitochondrial fatty acid oxidation (FAO) has been proposed to be a major bioenergetic pathway in prostate cancer. However, this concept fails to consider FAO relative to other mitochondrial substrates. Here, we found extracellular long-chain fatty acids (LCFAs), including palmitate, stearate, oleate, linoleate, linolenate, are minor sources of carbon entering the TCA cycle compared to glucose and glutamine in prostate cancer cells, despite being assimilated in the mitochondria as acyl-carnitines. In contrast, cardiolipins were a prominent LCFAs sink, with some species achieving greater than 50% 13C-labelling within 6 hours, suggesting high cardiolipin turnover using extracellular LCFAs. Knockdown of CPT1a, the rate-limiting enzyme of LCFA entry into mitochondria, reduced the incorporation of extracellular linoleate into cardiolipins. These results demonstrate that FAO is not a major input for the TCA cycle and provide evidence for an underappreciated role for CPT1a in regulating LCFAs entry into mitochondria for cardiolipin remodelling.
Matching journals
The top 2 journals account for 50% of the predicted probability mass.
Similar papers in this journal
- Serine catabolism generates NADPH to support hepatic lipogenesis 97%
- Hexokinase detachment from mitochondria drives the Warburg effect to support compartmentalized ATP production 97%
- Mitochondrial complex III-derived ROS amplify immunometabolic changes in astrocytes and promote dementia pathology 95%
Similar papers in this journal
Similar papers in this journal
Similar papers in this journal
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.