Lactate dehydrogenase supports lactate oxidation in mitochondria isolated from different mouse tissues, 2019, Young et al

[Andy]

Highlights

• Lactate can fuel mitochondrial respiration.
• Lactate serves as a substrate for H2O2 production.
• Mitochondria contain LDH.

Abstract
Research over the past seventy years has established that mitochondrial-l-lactate dehydrogenase (m-L-LDH) is vital for mitochondrial bioenergetics. However, in recent report, Fulghum et al. concluded that lactate is a poor fuel for mitochondrial respiration [1]. In the present study, we have followed up on these findings and conducted an independent investigation to determine if lactate can support mitochondrial bioenergetics. We demonstrate herein that lactate can fuel the bioenergetics of heart, muscle, and liver mitochondria. Lactate was just as effective as pyruvate at stimulating mitochondrial coupling efficiency. Inclusion of LDH (sodium oxamate or GSK 2837808A) and pyruvate dehydrogenase (PDH; CPI-613) inhibitors abolished respiration in mitochondria energized with lactate. Lactate also fueled mitochondrial ROS generation and was just as effective as pyruvate at stimulating H2O2 production. Additionally, lactate-induced ROS production was inhibited by both LDH and PDH inhibitors. Enzyme activity measurements conducted on permeabilized mitochondria revealed that LDH is localized in mitochondria. In aggregate, we can conclude that mitochondrial LDH fuels bioenergetics in several tissues by oxidizing lactate.

Open access, https://www.sciencedirect.com/science/article/pii/S2213231719311176

 

[lansbergen]

Lactate serves as a substrate for H2O2 production.

H2O2 can destroy pathogens.

 

[sb4]

@Andy I remember reading somewhere that 2 pyruvate are required to enter the mito and operate the PDC. One gets turned into Acetyl-CoA and in turn produces NADH, the other pyruvate uses the generated NADH with LDH to turn into lactate, regenerating the NAD+ so that the 2 new Pyruvates can enter the TCA and repeat the process. Therefore the healthy ratio between pyruvate and lactate (in the mitochondria I presume) is 1:1.

I think it would be possible that in a subset of ill people, that for whatever reason lots more lactate is being produced in comparison to pyruvate being oxidized resulting from burning muscles upon slight exertion that isn't anything to do with deconditioning (I experience this).

Does the study address this? Perhaps if you add some lactate then pyruvate can compensate and maintain a healthy ratio whilst stimulating more mito activity but then at some threshold the lactate becomes a negative.

 

[Andy]

Does the study address this? Perhaps if you add some lactate then pyruvate can compensate and maintain a healthy ratio whilst stimulating more mito activity but then at some threshold the lactate becomes a negative.

I've not the brain or science knowledge to answer you specifically, but my general comments are:

* this isn't an ME/CFS specific study. They say

However, in a recent report published in Redox Biology, Fulghum et al. concluded that lactate cannot fuel the bioenergetics of striated muscle due to the absence of m-L-LDH [1]. These findings directly contradict previous studies showing that lactate can fuel mitochondria in striated muscle and various other tissues as well as a myriad of cell types [9,[17], [18], [19], [20], [21], [22], [23]]. Using the guide supplied by Passarella et al., we counter the conclusions drawn by Fulghum et al. and demonstrate that mitochondria oxidize lactate [13].

so this study has been done to counter a previous one which claimed that lactate can't be/isn't used as a fuel.

* I've posted it because it discussed things of general interest to us, i.e. mitochondria, lactate and reactive oxygen species (ROS), and my thought was that, theoretically, it could be we see an increase in lactate because it's not being consumed in the same way that it is in someone healthy, rather than we are generating more than normal.

* They say

We also conducted experiments using reaction mixtures containing CPI-613, an inhibitor for α-keto acid dehydrogenases like pyruvate dehydrogenase, to determine if it can also abolish lactate-supported respiration. Inclusion of CPI-613 almost abolished lactate-stimulated O2 consumption by heart and muscle mitochondria

which certainly seems interesting to me given that pyruvate dehydrogenase has been found to be inhibited by Fluge and Mella, although they, to my knowledge, didn't identify the cause.

Hope that helps some?