Open Access
Metabolic inflexibility promotes mitochondrial health during liver regeneration
Xun Wang
1
,
Cameron J. Menezes
1
,
Yuemeng Jia
1
,
Yi Xiao
1
,
Siva Sai Krishna Venigalla
1
,
Feng Cai
1
,
Meng Hsiung Hsieh
1
,
Wen Gu
1
,
Liming Du
1
,
Jessica Sudderth
1
,
Dohun Kim
1
,
Spencer D Shelton
1
,
Claire B. Llamas
1
,
Yu Hsuan Lin
1
,
Min Zhu
1
,
Salma Merchant
1
,
Divya Bezwada
1
,
Sherwin Kelekar
1
,
Lauren G. Zacharias
1
,
THOMAS MATHEWS
1
,
Gerta Hoxhaj
1, 2
,
R. Max Wynn
3
,
Uttam K. Tambar
3
,
Ralph J. DeBerardinis
1, 2, 4, 5
,
Hao Zhu
1, 2, 4, 6, 7
,
Prashant Mishra
1, 2, 4
2
3
5
Publication type: Journal Article
Publication date: 2024-06-14
scimago Q1
wos Q1
SJR: 10.416
CiteScore: 48.4
Impact factor: 45.8
ISSN: 00368075, 10959203
PubMed ID:
38870309
Abstract
Mitochondria are critical for proper organ function and mechanisms to promote mitochondrial health during regeneration would benefit tissue homeostasis. We report that during liver regeneration, proliferation is suppressed in electron transport chain (ETC)–dysfunctional hepatocytes due to an inability to generate acetyl-CoA from peripheral fatty acids through mitochondrial β-oxidation. Alternative modes for acetyl-CoA production from pyruvate or acetate are suppressed in the setting of ETC dysfunction. This metabolic inflexibility forces a dependence on ETC-functional mitochondria and restoring acetyl-CoA production from pyruvate is sufficient to allow ETC-dysfunctional hepatocytes to proliferate. We propose that metabolic inflexibility within hepatocytes can be advantageous by limiting the expansion of ETC-dysfunctional cells.
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Metrics
31
Total citations:
31
Citations from 2024:
31
(100%)
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RIS |
BibTex
Cite this
GOST
Copy
Wang X. et al. Metabolic inflexibility promotes mitochondrial health during liver regeneration // Science. 2024. Vol. 384. No. 6701.
GOST all authors (up to 50)
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Wang X., Menezes C. J., Jia Y., Xiao Y., Venigalla S. S. K., Cai F., Hsieh M. H., Gu W., Du L., Sudderth J., Kim D., Shelton S. D., Llamas C. B., Lin Yu. H., Zhu M., Merchant S., Bezwada D., Kelekar S., Zacharias L. G., MATHEWS T., Hoxhaj G., Wynn R. M., Tambar U. K., DeBerardinis R. J., Zhu H., Mishra P. Metabolic inflexibility promotes mitochondrial health during liver regeneration // Science. 2024. Vol. 384. No. 6701.
Cite this
RIS
Copy
TY - JOUR
DO - 10.1126/science.adj4301
UR - https://www.science.org/doi/10.1126/science.adj4301
TI - Metabolic inflexibility promotes mitochondrial health during liver regeneration
T2 - Science
AU - Wang, Xun
AU - Menezes, Cameron J.
AU - Jia, Yuemeng
AU - Xiao, Yi
AU - Venigalla, Siva Sai Krishna
AU - Cai, Feng
AU - Hsieh, Meng Hsiung
AU - Gu, Wen
AU - Du, Liming
AU - Sudderth, Jessica
AU - Kim, Dohun
AU - Shelton, Spencer D
AU - Llamas, Claire B.
AU - Lin, Yu Hsuan
AU - Zhu, Min
AU - Merchant, Salma
AU - Bezwada, Divya
AU - Kelekar, Sherwin
AU - Zacharias, Lauren G.
AU - MATHEWS, THOMAS
AU - Hoxhaj, Gerta
AU - Wynn, R. Max
AU - Tambar, Uttam K.
AU - DeBerardinis, Ralph J.
AU - Zhu, Hao
AU - Mishra, Prashant
PY - 2024
DA - 2024/06/14
PB - American Association for the Advancement of Science (AAAS)
IS - 6701
VL - 384
PMID - 38870309
SN - 0036-8075
SN - 1095-9203
ER -
Cite this
BibTex (up to 50 authors)
Copy
@article{2024_Wang,
author = {Xun Wang and Cameron J. Menezes and Yuemeng Jia and Yi Xiao and Siva Sai Krishna Venigalla and Feng Cai and Meng Hsiung Hsieh and Wen Gu and Liming Du and Jessica Sudderth and Dohun Kim and Spencer D Shelton and Claire B. Llamas and Yu Hsuan Lin and Min Zhu and Salma Merchant and Divya Bezwada and Sherwin Kelekar and Lauren G. Zacharias and THOMAS MATHEWS and Gerta Hoxhaj and R. Max Wynn and Uttam K. Tambar and Ralph J. DeBerardinis and Hao Zhu and Prashant Mishra},
title = {Metabolic inflexibility promotes mitochondrial health during liver regeneration},
journal = {Science},
year = {2024},
volume = {384},
publisher = {American Association for the Advancement of Science (AAAS)},
month = {jun},
url = {https://www.science.org/doi/10.1126/science.adj4301},
number = {6701},
doi = {10.1126/science.adj4301}
}