Dichloroacetate Stabilizes Mitochondrial Fusion Dynamics in Models of Neurodegeneration, 2019, O'Hara et al

Andy

Andy

Retired committee member
Mitochondrial dysfunction is a recognized hallmark of neurodegenerative diseases and abnormal mitochondrial fusion-fission dynamics have been implicated in the pathogenesis of neurodegenerative disorders. This study characterizes the effects of metabolic flux inhibitors and activators on mitochondrial fusion dynamics in the neuronal cell culture model of differentiated PC12 cells. Using a real time confocal microscopy assay, it was found that the carnitine palmitoyltransferase I (CPTI) inhibitor, etomoxir, reduced mitochondrial fusion dynamics in a time-dependent manner. Etomoxir also decreased JO2, ΔΨm and reactive oxygen species (ROS) production rates. The mitochondrial pyruvate carrier (MPC) inhibitor, UK5099, reduced fusion dynamics and in combination with etomoxir these inhibitory effects were amplified. Use of the pyruvate dehydrogenase (PDH) kinase inhibitor dichloroacetate, which is known to increase metabolic flux through PDH, reversed the etomoxir-induced effects on fusion dynamics, JO2, ΔΨm but not ROS production rates. Dichloroacetate also partially reversed inhibition of mitochondrial fusion dynamics caused by the parkinsonian-inducing neurotoxin, MPP+. These results suggest that dichloroacetate-induced activation of metabolic flux in the mitochondrion may be a mechanism to restore normal mitochondrial fusion-fission dynamics in metabolically challenged cells.
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Open access, https://www.frontiersin.org/articles/10.3389/fnmol.2019.00219/full
 
Interesting. It appears some people had success with DCA over on PR but it did nothing for me.
 
mariovitali said:
I added dichloroacetate and several other related topics to mito fission/fysion/drp1 etc to see what we are getting.
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There are some patient stories on PR. It seems quite a few felt they developed neuropathy or thought their neuropathy got worse, despite taking B1 and ALA. So there is some significant risk.
https://forums.phoenixrising.me/thr...ichloroacetate-pilot-trial.58184/post-2222970

This papers states how DCA affects mitochondria (in mice)
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4359228/
Accordingly, preliminary results obtained by our group indicate a DCA-mediated change in the expression of factors known to be involved in the mitochondrial dynamics (i.e. up-regulation of Drp1, down-regulation of OPA1 and Mfn1; manuscript in preparation).
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Other articles talk about DCA having neuroprotective properties (whatever that means).

There is a thread here on s4me regarding an ME study of DCA where the author, a doctor, engaged in the thread. Unfortunately there is no discussion on possible mitochondria effects, instead its "stress" so unfortunately nothing of interest of a biological discussion in the comments
https://www.s4me.info/threads/treat...th-sodium-dichloroacetate-comhaire-2018.2885/

Lets see if you find anything interesting........
 
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