This research identifies SLC25A35 as the essential mitochondrial carrier protein responsible for exporting phosphoenolpyruvate (PEP) into the cytosol of lipogenic cells. While PEP is a high-energy metabolite traditionally associated with glucose production, these sources demonstrate that adipocytes primarily generate it within the mitochondria to drive the synthesis of glycerolipids. The study utilizes 13C-pyruvate tracing and liposome reconstitution to prove that SLC25A35 transports PEP in a process gated by mitochondrial membrane potential. Depleting this protein in fat cells impairs triglyceride production, whereas inhibiting it in the liver of obese mice successfully reduces fatty liver disease. Ultimately, the findings establish a direct link between mitochondrial energetics and lipid accumulation, suggesting a new therapeutic target for metabolic disorders like type 2 diabetes.

References:

• Yamamuro T, Katoh D, Silva G M, et al. Mitochondrial control of glycerolipid synthesis by a PEP shuttle[J]. Cell, 2026.