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Review
. 2022 Nov 4:13:1038421.
doi: 10.3389/fphys.2022.1038421. eCollection 2022.

Mutual regulation of lactate dehydrogenase and redox robustness

Yijun Lin  1 , Yan Wang  1 , Pei-Feng Li  1
Affiliations
Review

Mutual regulation of lactate dehydrogenase and redox robustness

Yijun Lin et al. Front Physiol. .

Abstract

The nature of redox is electron transfer; in this way, energy metabolism brings redox stress. Lactate production is associated with NAD regeneration, which is now recognized to play a role in maintaining redox homeostasis. The cellular lactate/pyruvate ratio could be described as a proxy for the cytosolic NADH/NAD ratio, meaning lactate metabolism is the key to redox regulation. Here, we review the role of lactate dehydrogenases in cellular redox regulation, which play the role of the direct regulator of lactate-pyruvate transforming. Lactate dehydrogenases (LDHs) are found in almost all animal tissues; while LDHA catalyzed pyruvate to lactate, LDHB catalyzed the reverse reaction . LDH enzyme activity affects cell oxidative stress with NAD/NADH regulation, especially LDHA recently is also thought as an ROS sensor. We focus on the mutual regulation of LDHA and redox robustness. ROS accumulation regulates the transcription of LDHA. Conversely, diverse post-translational modifications of LDHA, such as phosphorylation and ubiquitination, play important roles in enzyme activity on ROS elimination, emphasizing the potential role of the ROS sensor and regulator of LDHA.

Keywords: ROS; lactate; lactate dehydrogenases; post-translational modification; redox.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

FIGURE 1
FIGURE 1
Lactate metabolism and redox homeostasis. Glycolytic flux from glucose to pyruvate generates NADH from NAD at the GAPDH reaction, while LDHA-catalyzed pyruvate to lactate consumes NADH. The pyruvate–lactate ratio in some conditions reflects the NAD–NADH ratio. MCT-mediated proton-dependent lactate transport maintains the balance between intracellular and circulated lactate.
FIGURE 2
FIGURE 2
LDHA structure and modification. The 332-amino acid protein could be described as having three parts, N terminal domain, NADH-binding domain, and pyruvate-binding domain. There are five kinds of modifications that have been reported in different sites of LDHA, namely, phosphorylation, acetylation, methylation, ubiquitination, and succinylation.
FIGURE 3
FIGURE 3
LDH regulation in diseases and clinical translation.
See this image and copyright information in PMC

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