Science (New York, N.Y.)Oct 1, 2026

Mitochondrial transporter SLC25A34 connects body clock, diet, and temperature to fat cell fat cycling

Circadian Biology Weekly Brief ↗PubMed ↗DOI ↗

Updated Oct 3, 2026

Abstract

SLC25A34 is proposed to import oxaloacetate into mitochondria, linking circadian rhythms and dietary signals to lipid metabolism.

Circadian rhythms, diet, and environmental temperature influence adipocyte lipid metabolism.
During sleep, the adipocyte clock reduces the expression of Slc25a34 via specific transcriptional repressors.
Active periods, lipid-rich diets, and cold exposure remove the suppression of Slc25a34 expression.
Lipolytic signals can enhance Slc25a34 transcription through certain receptors.
SLC25A34 plays a role in supporting key metabolic processes, including the tricarboxylic acid cycle and lipid synthesis.

Simplified

Adipocyte lipid metabolism is coordinated by circadian rhythms, diet, and environmental temperature, but how these diverse signals are molecularly integrated remains unknown. We showed that these cues converge on the orphan mitochondrial transporter SLC25A34 to orchestrate lipid cycling. During the sleep phase, the adipocyte clock suppresses Slc25a34 expression through the REV-ERB transcriptional repressors. Entering the active phase, consuming lipid-rich diets, or exposure to cold abolishes REV-ERB repression, and lipolytic signals stimulate Slc25a34 transcription through the peroxisome proliferator-activated receptors. SLC25A34 is proposed to import oxaloacetate into mitochondria, dually supporting the tricarboxylic acid cycle and cytosolic acetyl-coenzyme A (acetyl-CoA) production. Elevated cytosolic acetyl-CoA then fuels the synthesis of lipids and promotes the transcription of genes enhancing mitochondrial oxidation. Thus, SLC25A34 confers circadian, dietary, and temperature control of adipocyte lipid metabolism.