Медицинская библиотека · bioRxiv : the preprint server for biology · 2026

Mitochondrial carrier SLC25A34 links clock, diet, and temperature control of interorganellar lipid cycling.

Karavaeva Iuliia, Basse Astrid Linde, Trammell Samuel A J, Hussain Mohammed Faiz, Markussen Lasse Kruse, Havelund Jesper F, Isidor Marie Sophie, Richter Hannah J, Chubanava Sabina, Deleye Yann, Kaiser Zafir, Shen Yachen, Neess Ditte, Sass Frederike, Finger Fabian, Muntadas Lidia Argemi, Tandio David, Ma Tao, Sustarsic Elahu Gosney, Embring Hannes, Kristensen Cecilie Kynding, McIntyre Rebecca L, Martinez Genesee J, Husted Anna Sofie, Emmett Matthew J, Kipp Zachary A, Frost Mikkel, Jedrychowski Mark P, van Weeghel Michel, Majd Homa, Zhuravleva Ekaterina, McGarrah Robert W, Plucinska Kaja, Midha Mohit K, Prokesch Andreas, Cohen Paul, Granneman James G, Seale Patrick, Houtkooper Riekelt H, Hansen Jacob B, Gygi Steven P, Schwartz Thue W, Gillum Matthew Paul, Hinds Terry D, Soccio Raymond Edward, White Phillip J, Kunji Edmund R S, Moritz Thomas, Treebak Jonas T, Mandrup Susanne, Emanuelli Brice, Kazak Lawrence, Færgeman Nils J, Lazar Mitchell A, Zachary Gerhart-Hines

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Аннотация

Adipocyte lipid metabolism is coordinated by circadian rhythms, diet, and environmental temperature. Yet how these diverse signals are molecularly integrated remains unknown. Here we show that clock, diet, and temperature cues converge on the orphan mitochondrial transporter, SLC25A34, to orchestrate thermogenic cycling of lipid synthesis and oxidation. During sleep, the clock suppresses Slc25a34 transcription through REV-ERBα. Waking, lipid-rich diets, or cold exposure abolish this repression, allowing lipolytic signals to stimulate Slc25a34 expression via PPARα. SLC25A34 then imports oxaloacetate into mitochondria to accelerate the export of substrates used for acetyl-CoA production in the cytosol. This feeds into cytosolic lipid synthesis and transcriptional induction of mitochondrial biogenesis, which collectively promote mitochondrial lipid oxidation. Thus, SLC25A34 confers circadian, dietary, and environmental control of thermogenic metabolism through interorganellar lipid cycling.

Для цитирования: Karavaeva Iuliia, Basse Astrid Linde, Trammell Samuel A J, Hussain Mohammed Faiz, Markussen Lasse Kruse, Havelund Jesper F, Isidor Marie Sophie, Richter Hannah J, Chubanava Sabina, Deleye Yann, Kaiser Zafir, Shen Yachen, Neess Ditte, Sass Frederike, Finger Fabian, Muntadas Lidia Argemi, Tandio David, Ma Tao, Sustarsic Elahu Gosney, Embring Hannes, Kristensen Cecilie Kynding, McIntyre Rebecca L, Martinez Genesee J, Husted Anna Sofie, Emmett Matthew J, Kipp Zachary A, Frost Mikkel, Jedrychowski Mark P, van Weeghel Michel, Majd Homa, Zhuravleva Ekaterina, McGarrah Robert W, Plucinska Kaja, Midha Mohit K, Prokesch Andreas, Cohen Paul, Granneman James G, Seale Patrick, Houtkooper Riekelt H, Hansen Jacob B, Gygi Steven P, Schwartz Thue W, Gillum Matthew Paul, Hinds Terry D, Soccio Raymond Edward, White Phillip J, Kunji Edmund R S, Moritz Thomas, Treebak Jonas T, Mandrup Susanne, Emanuelli Brice, Kazak Lawrence, Færgeman Nils J, Lazar Mitchell A, Zachary Gerhart-Hines. Mitochondrial carrier SLC25A34 links clock, diet, and temperature control of interorganellar lipid cycling.. bioRxiv : the preprint server for biology. 2026. DOI: 10.64898/2026.05.30.724257.

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