Overexpression of UCP3 decreases mitochondrial efficiency in mouse skeletal muscle in vivo. Issue 2 (27th September 2022)

• Record Type: Journal Article
• Authors: Codella, Roberto; Alves, Tiago C.; Befroy, Douglas E.; Choi, Cheol Soo; Luzi, Livio; Rothman, Douglas L.; Kibbey, Richard G.; Shulman, Gerald I.
• Is Part Of: FEBS letters. Volume 597:Issue 2(2023)
• Page Start: 309
• Page End: 319
• Publication Date: 2022-09-27
• Subjects: magnetic resonance spectroscopy -- mitochondrial efficiency -- mitochondrial uncoupling -- muscle energy metabolism; Biochemistry -- Periodicals; Biophysics -- Periodicals; Molecular biology -- Periodicals; Biochimie -- Périodiques; Biochemistry; Biophysics; Molecular biology; Periodicals; 572.05
• DOI: 10.1002/1873-3468.14494
• Languages: English
• ISSNs: 0014-5793

Abstract

Abstract : Uncoupling protein‐3 (UCP3) is a mitochondrial transmembrane protein highly expressed in the muscle that has been implicated in regulating the efficiency of mitochondrial oxidative phosphorylation. Increasing UCP3 expression in skeletal muscle enhances proton leak across the inner mitochondrial membrane and increases oxygen consumption in isolated mitochondria, but its precise function in vivo has yet to be fully elucidated. To examine whether muscle‐specific overexpression of UCP3 modulates muscle mitochondrial oxidation in vivo, rates of ATP synthesis were assessed by 31 P magnetic resonance spectroscopy (MRS), and rates of mitochondrial oxidative metabolism were measured by assessing the rate of [2‐ 13 C]acetate incorporation into muscle [4‐ 13 C]‐, [3‐ 13 C]‐glutamate, and [4‐ 13 C]‐glutamine by high‐resolution 13 C/ 1 H MRS. Using this approach, we found that the overexpression of UCP3 in skeletal muscle was accompanied by increased muscle mitochondrial inefficiency in vivo as reflected by a 42% reduction in the ratio of ATP synthesis to mitochondrial oxidation. Abstract : To examine whether uncoupling protein‐3 (UCP3) modulates muscle mitochondrial metabolism in vivo, oxidative phosphorylation was assessed in the hindlimb of anesthetized control and UCP3‐overexpressing mice by determining (a) the rates of substrate oxidation via the tricarboxylic acid cycle, using [2‐ 13 C]‐acetate, and (b) the rates of ATP synthesis, using 31 P‐magnetic resonance spectroscopy. UCP3 overexpression resulted in a 42% decrease in muscle mitochondrial efficiency.