Mpc1, a key component of the mitochondrial pyruvate carrier, controls pyruvate transportation into mitochondria. This process links glycolysis and the TCA cycle, playing a vital role in energy production and various metabolic pathways. Genetic models, like gene knockout mouse models, are valuable for studying Mpc1's functions [1,2,5,6,8-10].

In NAFLD, Mpc1 expression positively correlates with liver lipid deposition. Mpc1+/- mice on a high-fat diet show reduced hepatic lipid accumulation, and Mpc1 knockout affects fatty acid synthase lactylation, which inhibits its activity and liver lipid accumulation. In addition, Mpc1 knockout also controls the inflammation level through mitochondrial protection and macrophage polarization [1].

In lung adenocarcinoma, Mpc1 is lowly expressed and suppresses stemness, invasion, and migration. Its deficiency accelerates the disease progression through the STAT3 pathway [2].

In cervical cancer, low Mpc1 expression is associated with shorter overall survival, and it is related to immune infiltration and the ferroptosis pathway [3].

In glioblastoma, Mpc1 deletion is linked to poor prognosis and temozolomide resistance [4].

In cardiomyocytes, genetic ablation of Mpc1 induces hypertrophy and heart failure, while overexpression attenuates drug-induced hypertrophy [5].

In CRC, Mpc1 deficiency promotes liver metastasis by facilitating nuclear translocation of β-catenin [6].

In terminally exhausted CD8+ T cells, upregulating Mpc1-dependent oxidative phosphorylation can revitalize these cells [7].

In renal cell carcinoma, low PGC-1α expression reduces Mpc1 expression, impairing mitochondrial respiratory capacity [8].

Pathogenic Mpc1 variants lead to mitochondrial pyruvate carrier deficiency, presenting with developmental delay, microcephaly, etc. [9].

Retina-specific deletion of Mpc1 causes progressive retinal degeneration and visual function decline [10].

In conclusion, Mpc1 is essential for mitochondrial pyruvate usage, energy metabolism, and various biological processes. Studies using Mpc1 KO/CKO mouse models have revealed its significant roles in multiple diseases, including NAFLD, various cancers, heart failure, and mitochondrial and retinal diseases, providing insights into disease mechanisms and potential therapeutic targets.