2018
DOI: 10.1139/apnm-2017-0450
|View full text |Cite
|
Sign up to set email alerts
|

Lactate is oxidized outside of the mitochondrial matrix in rodent brain

Abstract: Abstract:The nature and existence of mitochondrial lactate oxidation is debated in the literature. Obscuring the issue are disparate findings in isolated mitochondria, as well as relatively low rates of lactate oxidation observed in permeabilized muscle fibres. However, respiration with lactate has yet to be directly assessed in brain tissue with the mitochondrial reticulum intact. To determine if lactate is oxidized in the matrix of brain mitochondria, oxygen consumption was measured in saponinpermeabilized m… Show more

Help me understand this report

Search citation statements

Order By: Relevance

Paper Sections

Select...
2
1
1

Citation Types

1
8
0

Year Published

2018
2018
2024
2024

Publication Types

Select...
5
1

Relationship

0
6

Authors

Journals

citations
Cited by 9 publications
(9 citation statements)
references
References 52 publications
1
8
0
Order By: Relevance
“…ECII increased with age equally in WT and Tg21 (P3 and P7 less than P14, P21 and P60; 1-RM ANOVA, F(4,66) = 8.078, p < 0.0001). Observed agespecific measures from both genotypes are similar to [28][29][30] or higher than 31 analogous respiratory state OCRs previously reported when respiring brain samples from C57BL/6 mice and/or Winstar rats. Collectively, this data suggests that the overexpression of EPO in the hippocampus facilitates greater respiratory capacity earlier in postnatal development compared to WT controls, having a peak at P21.…”
supporting
confidence: 80%
“…ECII increased with age equally in WT and Tg21 (P3 and P7 less than P14, P21 and P60; 1-RM ANOVA, F(4,66) = 8.078, p < 0.0001). Observed agespecific measures from both genotypes are similar to [28][29][30] or higher than 31 analogous respiratory state OCRs previously reported when respiring brain samples from C57BL/6 mice and/or Winstar rats. Collectively, this data suggests that the overexpression of EPO in the hippocampus facilitates greater respiratory capacity earlier in postnatal development compared to WT controls, having a peak at P21.…”
supporting
confidence: 80%
“…These results are aligned with increasing evidence that metabolites derived from glycolytic metabolism, rather than glutamine, often supply TCA metabolism in-vivo 32,58 . Recent evidence suggests glucose can feed the TCA via circulating lactate 37,38 , and while our in-vivo experiments do not allow us to differentiate between glucose and lactate as the carbon source that is actually entering the tumor, the distinction may become inconsequential because glucose and lactate are primarily converted to pyruvate prior to mitochondrial entry via the MPC 39 . Indeed, MPC inhibition in PCa cells suppressed lactate oxidation in our models and is known to interrupt lactate uptake in models of cervical, pharyngeal, and breast cancer 41 .…”
Section: Discussionmentioning
confidence: 83%
“…Last, accumulating evidence suggests lactate is an important carbon source for tumor TCA metabolism in-vivo 37,38 . Exogenous lactate must be converted to pyruvate prior to oxidation in the TCA, but it is not clear if pyruvate is converted in the cytosol or the mitochondrial matrix and there is evidence for both 39,40 . However, in agreement with a recent report 41 , we found MPC inhibition in our models prevented lactate oxidation (Supplementary Fig.…”
Section: Resultsmentioning
confidence: 99%
“…However, a recent radioisotope labeling study in mice determined that circulating lactate turnover was the highest of all blood metabolites, resulting in labeling of a variety of TCA cycle intermediates in all tissues tested ( 82 , 115 ). Additionally, mitochondria isolated from many cells and tissues have been shown to oxidize lactate at rates that are similar to (or greater than) pyruvate ( 111 , 116 , 117 , 118 ). Lactate dehydrogenase reactions tend to favor lactate formation from pyruvate at equilibrium under physiological conditions (ΔG°’ LDH = −23.4 kJ mol −1 ) and LDH isoforms generally exhibit high activity ( 111 ).…”
Section: Interpreting Bioenergetics Experimentsmentioning
confidence: 99%
“…Second, as mentioned above, lactate produced from homolactic fermentation may be oxidized in mitochondria, which would have the effect of “uncoupling” J H + from glycolytic flux. Whether or not a given cell type retains the ability to oxidize lactate in support of cellular respiration is testable using isolated mitochondria or permeabilized cell preparations ( 111 , 116 ). Unfortunately, controlling for the magnitude of this effect in the intact cell to correct the ECAR measurement does not appear to be possible without altering the integration of OxPhos and glycolysis, because inhibiting lactate oxidation would likely alter glycolytic flux.…”
Section: Interpreting Bioenergetics Experimentsmentioning
confidence: 99%