Mitochondrial Transport and Metabolic Integration: Revisiting the Role of Metabolite Trafficking in Cellular Bioenergetics

Mitochondria serve as central hubs of cellular metabolism, integrating catabolic and anabolic pathways through the controlled exchange of metabolites across their membranes. Although mitochondrial transport of several metabolites has been well documented, the mechanisms underlying the trafficking of fumarate, glutamine, and phosphoenolpyruvate as well as the role of the mitochondrial pyruvate kinase remain insufficiently represented in modern biochemistry textbooks. Here, we revisit the biochemical evidence supporting specific transport systems for these metabolites, discuss their physiological roles in major metabolic pathways, and highlight how foundational experimental studies have been overlooked in contemporary literature. Re-examining these mechanisms provides new insight into the dynamic interplay between mitochondrial function, cytosolic metabolism, and overall cellular homeostasis.