Mutual regulation of lactate dehydrogenase and redox robustness

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.

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“…We speculated that this was attributed to the fact that resveratrol enhances the activity of muscle LDH enzyme (Fig. 2C), and previous study have shown that the enhanced activity of LDH enzyme can make mitochondria produce low demand for ATP through oxidative phosphorylation, avoiding the increase of ROS in mitochondria [41]. SLC25A4S, one of mitochondrial permeability transition pore (mPTP), plays an important role in a pathway for •O 2− to exit the mitochondria [47].…”

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“…The two most common proteins are LDHA and LDHB, with LDHC being the third subunit that has been shown to be distributed in germ cells [ 36 ]. Recent studies have focused on the functions of LDH in cancer and metabolic syndromes, including diabetes [ 37 ]. Elevated glycolysis is a primary characteristic of osteoclast differentiation, as glucose is the primary energy source in osteoclasts [ 19 ].…”

AGS Gastric Cells: Antioxidant Activity and Metabolic Effects of Phenolic Extracts from Different Monocultivar Virgin Olive Oils

“…Through the catalytic action of LDHA (reduction of pyruvate to lactate by oxidation of NADH to NAD + ) and LDHB (oxidation of lactate to pyruvate by reduction of NAD + to NADH), the NADH/NAD + ratio is checked (regulated) and then the cytoplasmic redox state of the cell. In addition, the presence of a specific lactate transporter in the inner membrane of the mitochondria allows lactate to be translocated from the cytoplasm to the mitochondrial matrix, where, thanks to LDHB, it is converted to pyruvate with the reduction of NADH, conditioning the mitochondrial redox state [51].…”