Glutamine sustains energy metabolism and alleviates liver injury in burn sepsis by promoting the assembly of mitochondrial HSP60-HSP10 complex via SIRT4 dependent protein deacetylation

作者全名："Yang, Yongjun; Chen, Qian; Fan, Shijun; Lu, Yongling; Huang, Qianyin; Liu, Xin; Peng, Xi"

作者地址："[Yang, Yongjun; Chen, Qian; Fan, Shijun; Lu, Yongling; Huang, Qianyin; Liu, Xin; Peng, Xi] Third Mil Med Univ, Army Med Univ, Southwest Hosp, Clin Med Res Ctr, Chongqing, Peoples R China; [Peng, Xi] Third Mil Med Univ, Southwest Hosp, State Key Lab Trauma Burns & Combined Injury, Army Med Univ, Chongqing, Peoples R China"

通信作者："Liu, X; Peng, X (通讯作者)，Third Mil Med Univ, Army Med Univ, Southwest Hosp, Clin Med Res Ctr, Chongqing, Peoples R China."

来源：REDOX REPORT

ESI学科分类：BIOLOGY & BIOCHEMISTRY

WOS号：WOS:001159646700001

JCR分区：Q2

影响因子：3.8

年份：2024

卷号：29

期号：1

开始页：　

结束页：　

文献类型：Article

关键词：Glutamine; burn sepsis; HSP60-HSP10 assembly; energy metabolism; mitochondrial electron transport chain; reactive oxygen species; Sirtuin 4; liver injury

摘要："Burns and burn sepsis, characterized by persistent and profound hypercatabolism, cause energy metabolism dysfunction that worsens organ injury and systemic disorders. Glutamine (Gln) is a key nutrient that remarkably replenishes energy metabolism in burn and sepsis patients, but its exact roles beyond substrate supply is unclear. In this study, we demonstrated that Gln alleviated liver injury by sustaining energy supply and restoring redox balance. Meanwhile, Gln also rescued the dysfunctional mitochondrial electron transport chain (ETC) complexes, improved ATP production, reduced oxidative stress, and protected hepatocytes from burn sepsis injury. Mechanistically, we revealed that Gln could activate SIRT4 by upregulating its protein synthesis and increasing the level of Nicotinamide adenine dinucleotide (NAD+), a co-enzyme that sustains the activity of SIRT4. This, in turn, reduced the acetylation of shock protein (HSP) 60 to facilitate the assembly of the HSP60-HSP10 complex, which maintains the activity of ETC complex II and III and thus sustain ATP generation and reduce reactive oxygen species release. Overall, our study uncovers a previously unknown pharmacological mechanism involving the regulation of HSP60-HSP10 assembly by which Gln recovers mitochondrial complex activity, sustains cellular energy metabolism and exerts a hepato-protective role in burn sepsis."

基金机构：National Natural Science Foundation of China10.13039/501100001809

基金资助正文：No Statement Available