Ketone bodies stimulate chaperone-mediated autophagy.
Level 5 - mechanism / opinion, no new human data
In vitro mechanistic laboratory study
PubMed 15883160 · doi:10.1074/jbc.M502456200
What was done
The authors tested whether physiological concentrations of ketone bodies induce chaperone-mediated autophagy (CMA). Cultured cells and isolated lysosomes were exposed to beta-hydroxybutyrate (BOH), acetoacetate, or control compounds (glycerol, butanol, butanone) in media with or without serum. Proteolysis was evaluated using CMA substrates glyceraldehyde-3-phosphate dehydrogenase (GAPDH) and ribonuclease A (RNase A). The study also measured levels of CMA-associated proteins (LAMP-2A and lysosomal Hsc70) and assessed substrate oxidation via OxyBlot detection of protein carbonyls.
What was found
The abstract reports directional findings without numerical values, effect sizes, or statistical metrics. BOH induced proteolysis in cells maintained with or without serum, whereas acetoacetate did so only in serum-containing media. Isolated lysosomes from BOH-treated cells or reactions directly supplemented with BOH degraded GAPDH and RNase A more rapidly, without altering LAMP-2A or lysosomal Hsc70 protein levels. Pretreatment of substrate proteins with BOH increased their carbonyl oxidation and lysosomal degradation rate, while pretreating lysosomes alone had no effect. Glycerol, butanol, and butanone did not alter CMA activity.
Why it matters
This study outlines a biochemical mechanism linking starvation-induced ketone bodies to chaperone-mediated autophagy activation via direct substrate oxidation.
Limits
The study is restricted entirely to cell-free and in vitro cell culture preparations, with no in vivo animal or human data. The abstract reports no numerical measurements, exact ketone concentrations, sample sizes, experimental replicates, or specific cell lines.
Cited by
- partial Chaperone-mediated autophagy is deeply activated after 2.5 to 3 days of fasting.