Mitochondrial Transport in Glycolysis and Gluconeogenesis: Achievements and Perspectives

Abstract

Some metabolic pathways involve two different cell components, for instance, cytosol and mitochondria, with metabolites traffic occurring from cytosol to mitochondria and vice versa, as seen in both glycolysis and gluconeogenesis. However, the knowledge on the role of mitochondrial transport within these two glucose metabolic pathways remains poorly understood, due to controversial information available in published literature. In what follows, we discuss achievements, knowledge gaps, and perspectives on the role of mitochondrial transport in glycolysis and gluconeogenesis. We firstly describe the experimental approaches for quick and easy investigation of mitochondrial transport, with respect to cell metabolic diversity. In addition, we depict the mitochondrial shuttles by which NADH formed in glycolysis is oxidized, the mitochondrial transport of phosphoenolpyruvate in the light of the occurrence of the mitochondrial pyruvate kinase, and the mitochondrial transport and metabolism of L-lactate due to the L-lactate translocators and to the mitochondrial L-lactate dehydrogenase located in the inner mitochondrial compartment.

Aerobic Glycolysis: A DeOxymoron of (Neuro)Biology

“…The scenario wherein pyruvate is the end product of aerobic glycolysis was formulated when the glycolytic pathway was elucidated eight decades ago. Nevertheless, the part of the hypothesis that assumes 'aerobic glycolysis' to end up with lactate is in full agreement with the claim that L-lactate is always the end product of the glycolytic pathway under both anaerobic and aerobic conditions and, under the latter, the substrate of oxphos [34][35][36][37][38]. A recent review summarizes the overwhelming evidence supporting the existence of a mitochondrial lactate dehydrogenase (mLDH), which is responsible for the conversion of L-lactate to pyruvate intramitochondrially [38].…”

“…Nevertheless, the part of the hypothesis that assumes 'aerobic glycolysis' to end up with lactate is in full agreement with the claim that L-lactate is always the end product of the glycolytic pathway under both anaerobic and aerobic conditions and, under the latter, the substrate of oxphos [34][35][36][37][38]. A recent review summarizes the overwhelming evidence supporting the existence of a mitochondrial lactate dehydrogenase (mLDH), which is responsible for the conversion of L-lactate to pyruvate intramitochondrially [38]. L-lactate formation upon neural activation (stimulation) was clearly recorded by Hu and Wilson [21] (Figure 1); these results have been analyzed and discussed previously [31,32].…”

Sensitive monitoring of NAD(P)H levels within cancer cells using mitochondria-targeted near-infrared cyanine dyes with optimized electron-withdrawing acceptors

“…Glucose provides energy for cells via metabolic pathways like the citric acid cycle, glycolysis, and oxidative phosphorylation. 42 In the course of glucose metabolism, NADH is generated and acts as a vital electron contributor in the electron transport chain within the citric acid cycle, culminating in ATP synthesis—the cell's fundamental energy unit. Hence, the presence of glucose and its subsequent metabolism influence cellular NADH levels.…”

A Review of Research on the Association between Neuron–Astrocyte Signaling Processes and Depressive Symptoms

“…Often in the absence of neural activation, a large rise in lactate in the brain is likely to be a symptom of pathology. To illustrate, increased lactate levels in the blood, brain, and cerebrospinal fluid (CSF) were used as indicators of mitochondrial dysfunction [ 137 , 138 ]. This is because lactate does not accumulate in the brain or CSF when mitochondrial metabolism is intact; whereas, when mitochondrial dysfunction occurs, intracerebral metabolism switches to extramitochondrial glycolysis, and the lactate produced by glycolysis cannot be completely eliminated by mitochondrial metabolism, leading to lactate accumulation [ 139 , 140 ].…”