Metabolically induced intracellular pH changes activate mitophagy, autophagy, and cell protection in familial forms of Parkinson's disease.
Level 5 - mechanism / opinion, no new human data
In vitro human cell culture and ex vivo rodent tissue laboratory study
PubMed 34528385 · doi:10.1111/febs.16198
What was done
Researchers examined whether inducing intracellular pH changes with millimolar concentrations of sodium pyruvate and sodium lactate could activate autophagy and mitophagy in human fibroblasts bearing familial Parkinson's disease (PD) mutations (Pink1, Pink1/Park2, α-synuclein triplication, and A53T) and in acute brain slices from wild-type and Pink1 knockout mice.
What was found
Both lactate and pyruvate at millimolar concentrations induced transient cytosolic acidification in control and mutant human fibroblasts, leading to increased autophagy and mitophagy and protection against cell death. In acute brain slices from wild-type and Pink1 knockout mice, lactate reduced pH within neurons and astrocytes and elevated mitophagy. The abstract reports no specific numerical values, effect sizes, or statistical metrics.
Why it matters
This study identifies metabolic acidification of the cytosol as a potential mechanism to stimulate cellular clearance pathways and protect vulnerable cells in genetic models of Parkinson's disease.
Limits
The study is limited to in vitro patient-derived fibroblasts and ex vivo rodent brain slices, lacking in vivo testing in living animal models or humans. The abstract does not report sample sizes, specific concentrations, effect magnitudes, or variance data.
Cited by
- supports In worm and mouse models of Parkinson's disease, lactate administration enhances mitochondrial function and increases cell viability.