Ambre M. Bertholet, PhD

Dr. Bertholet's laboratory studies how mitochondria distribute energy between ATP and heat, and how a fine balance between these two forms of energy could support and influence cellular metabolism. They have identified the ADP/ATP carrier (AAC) as the main protein responsible for mitochondrial thermogenesis in non-adipose tissue. They have also discovered that common mitochondrial uncouplers, small molecules that increase mitochondrial heat production and are used to combat metabolic syndrome, target AAC. Interestingly, some chemical uncouplers are currently undergoing clinical trials for cancer. By exploring the role of mitochondrial heat production in cellular metabolism, they aim to control cellular metabolic needs as a potential target for cancer cells.

Bertholet A.M. *, Natale A.M. *, Bisignano P., Suzuki J., Fedorenko A., Hamilton J., Brustovetsky T., Kazak L., Garrity R., Chouchani E.T., Brustovetsky N., Grabe M.*, and Kirichok Y.*. (2022) Mitochondrial Uncouplers Induce Proton Leak by Activating AAC and UCP1. Nature 606(7912):180-187.

Chang C.F., Gunawan A.L., Liparulo I., Zushin P.H., Bertholet A.M., Kirichok Y., Stahl A. (2022) CoQ Regulates Brown Adipose Tissue Respiration and Uncoupling Protein 1 Expression. Antioxidants 12(1):14.

Skinner W.M., Petersen N.T., Unger B., Tang S., Tabarsi E., Lamm J., Jalalian L., Smith J., Bertholet A.M., Xu K., Kirichok Y., Lishko P.V. (2023) Mitochondrial uncouplers impair human sperm motility without altering ATP content. Biology of Reproduction ioad064.

Acevedo A., Jones A.E., Dana B.T., Turner R., Montales K.R., Benincá C., Reue K., Shirihai O.S., Wallace M., Wang Y., Bertholet A.M., Divakaruni A.S. (2024) The BCKDK inhibitor BT2 is a chemical uncoupler that lowers mitochondrial ROS production and de novo lipogenesis. J Biol Chem, Mar;300(3):105702.

Shimanaka Y., Tol M.J., Rocha C.R., Jellinek. M.J., Cui L., Bender A., Bedard A.H., Milner M.G., Melillo B., Williams K.J., Stiles L., Weston T.A., Cohn W., Whitelegge J.P., Bertholet A.M., Cravatt B.F., Young S.G., Houten S.M., Argmann C., Ford D.A., Liesa M., Shirihai O.S., Vanni S., Tontonoz P. (2025) A cold-inducible phospholipid– protein interaction in brown fat mitochondria optimizes thermogenic capacity. bioRxiv [Preprint]. 2025 May.