Local GHR roles in regulation of mitochondrial function through mitochondrial biogenesis during myoblast differentiation

Bowen Hu; Changbin Zhao; Xiangchun Pan; Haohui Wei; Guodong Mo; Mingjian Xian; Wen Luo; Qinghua Nie; Hongmei Li; Xiquan Zhang

doi:10.1186/s12964-023-01166-5

Local GHR roles in regulation of mitochondrial function through mitochondrial biogenesis during myoblast differentiation

Cell Commun Signal. 2023 Jun 19;21(1):148. doi: 10.1186/s12964-023-01166-5.

Authors

Bowen Hu^{1

2

3}, Changbin Zhao^{1

2

3}, Xiangchun Pan³, Haohui Wei^{1

2

3}, Guodong Mo^{1

2

3}, Mingjian Xian^{1

2

3}, Wen Luo^{1

2

3}, Qinghua Nie^{1

2

3}, Hongmei Li^{1

2

3}, Xiquan Zhang^{4

5

6}

Affiliations

¹ State Key Laboratory of Livestock and Poultry Breeding, South China Agricultural University, Guangzhou, Guangdong, China.
² State Key Laboratory for Conservation and Utilization of Subtropical Agro-Bioresources and Lingnan Guangdong Laboratory of Agriculture, South China Agricultural University, Guangzhou, Guangdong, China.
³ Department of Animal Genetics, Breeding and Reproduction, College of Animal Science, South China Agricultural University, Guangzhou, Guangdong, China.
⁴ State Key Laboratory of Livestock and Poultry Breeding, South China Agricultural University, Guangzhou, Guangdong, China. xqzhang@scau.edu.cn.
⁵ State Key Laboratory for Conservation and Utilization of Subtropical Agro-Bioresources and Lingnan Guangdong Laboratory of Agriculture, South China Agricultural University, Guangzhou, Guangdong, China. xqzhang@scau.edu.cn.
⁶ Department of Animal Genetics, Breeding and Reproduction, College of Animal Science, South China Agricultural University, Guangzhou, Guangdong, China. xqzhang@scau.edu.cn.

Abstract

Background: Myoblast differentiation requires metabolic reprogramming driven by increased mitochondrial biogenesis and oxidative phosphorylation. The canonical GH-GHR-IGFs axis in liver exhibits a great complexity in response to somatic growth. However, the underlying mechanism of whether local GHR acts as a control valve to regulate mitochondrial function through mitochondrial biogenesis during myoblast differentiation remains unknown.

Methods: We manipulated the GHR expression in chicken primary myoblast to investigate its roles in mitochondrial biogenesis and function during myoblast differentiation.

Results: We reported that GHR is induced during myoblast differentiation. Local GHR promoted mitochondrial biogenesis during myoblast differentiation, as determined by the fluorescence intensity of Mito-Tracker Green staining and MitoTimer reporter system, the expression of mitochondrial biogenesis markers (PGC1α, NRF1, TFAM) and mtDNA encoded gene (ND1, CYTB, COX1, ATP6), as well as mtDNA content. Consistently, local GHR enhanced mitochondrial function during myoblast differentiation, as determined by the oxygen consumption rate, mitochondrial membrane potential, ATP level and ROS production. We next revealed that the regulation of mitochondrial biogenesis and function by GHR depends on IGF1. In terms of the underlying mechanism, we demonstrated that IGF1 regulates mitochondrial biogenesis via PI3K/AKT/CREB pathway. Additionally, GHR knockdown repressed myoblast differentiation.

Conclusions: In conclusion, our data corroborate that local GHR acts as a control valve to enhance mitochondrial function by promoting mitochondrial biogenesis via IGF1-PI3K/AKT/CREB pathway during myoblast differentiation. Video Abstract.

Keywords: GHR; IGF1; Mitochondrial biogenesis; Mitochondrial function; Myoblast differentiation.

Publication types

Video-Audio Media
Research Support, Non-U.S. Gov't

MeSH terms

DNA, Mitochondrial / genetics
DNA, Mitochondrial / metabolism
Mitochondria / metabolism
Myoblasts / metabolism
Organelle Biogenesis*
Phosphatidylinositol 3-Kinases / metabolism
Proto-Oncogene Proteins c-akt* / metabolism

Substances

Proto-Oncogene Proteins c-akt
Phosphatidylinositol 3-Kinases
DNA, Mitochondrial