Abstract
As a nodal mediator of pyruvate metabolism, the mitochondrial pyruvate carrier (MPC) plays a pivotal role in many physiological and pathological processes across the human lifespan, from embryonic development to aging-associated neurodegeneration. Emerging research highlights the importance of the MPC in diverse conditions, such as immune cell activation, cancer cell stemness, and dopamine production in Parkinson’s disease models. Whether MPC function ameliorates or contributes to disease is highly specific to tissue and cell type. Cell- and tissue-specific differences in MPC content and activity suggest that MPC function is tightly regulated as a mechanism of metabolic, cellular, and organismal control. Accordingly, recent studies on cancer and diabetes have identified protein–protein interactions, post-translational processes, and transcriptional factors that modulate MPC function. This growing body of literature demonstrates that the MPC and other mitochondrial carriers comprise a versatile and dynamic network undergirding the metabolism of health and disease.
Highlights
The mitochondrial pyruvate carrier (MPC) was discovered in 2012 [1,2]
Mitochondrial pyruvate metabolism is controlled by a triumvirate of enzymes—the MPC, pyruvate dehydrogenase (PDH), and pyruvate carboxylase (PC) [6,7,8]—that together modulate many physiological and pathological processes
Some cancers exhibit increased MPC expression and predominantly rely on oxidative phosphorylation to support growth. This difference could be due to the metabolism of surrounding tumor tissue, tissue type, the oxygenation and blood supply of the tumor microenvironment, and the accessibility of immune cells, all of which affect the energy metabolism of a tumor and can determine whether the MPC is a mediator of pro- or anti-cancer effects
Summary
As early as 1971, studies predicted that a mitochondrial protein transported pyruvate from the cytoplasm into the mitochondria [3,4,5]. Smaller yet important niches for MPC research are becoming evident, highlighting the variety of situations where the MPC controls metabolism and dependent cellular functions. Some of these include embryonic and fetal health, stem cell development, neurogenerative disease, and immune cell function. Cell- and tissue-dependent differences in MPC content and activity suggest that MPC function is tightly regulated as a mechanism of metabolic, cellular, and organismal control. We examine MPC function across the lifespan, beginning with embryonic and fetal development and ending with aging-associated neurodegeneration
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