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Metabolic flexibility via mitochondrial BCAA carrier SLC25A44 is required for optimal fever.

Publication ,  Journal Article
Yoneshiro, T; Kataoka, N; Walejko, JM; Ikeda, K; Brown, Z; Yoneshiro, M; Crown, SB; Osawa, T; Sakai, J; McGarrah, RW; White, PJ; Nakamura, K ...
Published in: eLife
May 2021

Importing necessary metabolites into the mitochondrial matrix is a crucial step of fuel choice during stress adaptation. Branched chain-amino acids (BCAAs) are essential amino acids needed for anabolic processes, but they are also imported into the mitochondria for catabolic reactions. What controls the distinct subcellular BCAA utilization during stress adaptation is insufficiently understood. The present study reports the role of SLC25A44, a recently identified mitochondrial BCAA carrier (MBC), in the regulation of mitochondrial BCAA catabolism and adaptive response to fever in rodents. We found that mitochondrial BCAA oxidation in brown adipose tissue (BAT) is significantly enhanced during fever in response to the pyrogenic mediator prostaglandin E2 (PGE2) and psychological stress in mice and rats. Genetic deletion of MBC in a BAT-specific manner blunts mitochondrial BCAA oxidation and non-shivering thermogenesis following intracerebroventricular PGE2 administration. At a cellular level, MBC is required for mitochondrial BCAA deamination as well as the synthesis of mitochondrial amino acids and TCA intermediates. Together, these results illuminate the role of MBC as a determinant of metabolic flexibility to mitochondrial BCAA catabolism and optimal febrile responses. This study also offers an opportunity to control fever by rewiring the subcellular BCAA fate.

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Published In

eLife

DOI

EISSN

2050-084X

ISSN

2050-084X

Publication Date

May 2021

Volume

10

Start / End Page

e66865

Related Subject Headings

  • Thermogenesis
  • Rats
  • Mitochondrial Proteins
  • Mitochondria
  • Mice, Inbred C57BL
  • Mice
  • Male
  • Fever
  • Animals
  • Amino Acids, Branched-Chain
 

Citation

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Yoneshiro, T., Kataoka, N., Walejko, J. M., Ikeda, K., Brown, Z., Yoneshiro, M., … Kajimura, S. (2021). Metabolic flexibility via mitochondrial BCAA carrier SLC25A44 is required for optimal fever. ELife, 10, e66865. https://doi.org/10.7554/elife.66865
Yoneshiro, Takeshi, Naoya Kataoka, Jacquelyn M. Walejko, Kenji Ikeda, Zachary Brown, Momoko Yoneshiro, Scott B. Crown, et al. “Metabolic flexibility via mitochondrial BCAA carrier SLC25A44 is required for optimal fever.ELife 10 (May 2021): e66865. https://doi.org/10.7554/elife.66865.
Yoneshiro T, Kataoka N, Walejko JM, Ikeda K, Brown Z, Yoneshiro M, et al. Metabolic flexibility via mitochondrial BCAA carrier SLC25A44 is required for optimal fever. eLife. 2021 May;10:e66865.
Yoneshiro, Takeshi, et al. “Metabolic flexibility via mitochondrial BCAA carrier SLC25A44 is required for optimal fever.ELife, vol. 10, May 2021, p. e66865. Epmc, doi:10.7554/elife.66865.
Yoneshiro T, Kataoka N, Walejko JM, Ikeda K, Brown Z, Yoneshiro M, Crown SB, Osawa T, Sakai J, McGarrah RW, White PJ, Nakamura K, Kajimura S. Metabolic flexibility via mitochondrial BCAA carrier SLC25A44 is required for optimal fever. eLife. 2021 May;10:e66865.

Published In

eLife

DOI

EISSN

2050-084X

ISSN

2050-084X

Publication Date

May 2021

Volume

10

Start / End Page

e66865

Related Subject Headings

  • Thermogenesis
  • Rats
  • Mitochondrial Proteins
  • Mitochondria
  • Mice, Inbred C57BL
  • Mice
  • Male
  • Fever
  • Animals
  • Amino Acids, Branched-Chain