Regulation of Mitochondrial Metabolism by <i>Mfn1</i> Gene Encoding Mitofusin Affects Cellular Proliferation and Histone Modification

Mitochondria maintain cellular homeostasis through the dynamic balance of fusion and fission, which relies on nuclear-encoded mitochondrial fusion proteins, mitofusins 1 and 2 (Mfn1, Mfn2). Changes in <i>Mfn1</i> and <i>Mfn2</i> expression significantly affect mitochondrial f...

Full description

Saved in:
Bibliographic Details
Main Authors: Han Xu, Xiaoyu Zhao, Yuan Yun, Yuxin Gao, Chunjie Bo, Lishuang Song, Chunling Bai, Lei Yang, Guangpeng Li, Guanghua Su
Format: Article
Language:English
Published: MDPI AG 2025-07-01
Series:Cells
Subjects:
Online Access:https://www.mdpi.com/2073-4409/14/13/1015
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Mitochondria maintain cellular homeostasis through the dynamic balance of fusion and fission, which relies on nuclear-encoded mitochondrial fusion proteins, mitofusins 1 and 2 (Mfn1, Mfn2). Changes in <i>Mfn1</i> and <i>Mfn2</i> expression significantly affect mitochondrial fusion and fission, thereby affecting cellular metabolism. This study investigated the effect of <i>Mfn1</i> expression on cell proliferation, apoptosis, and mitochondrial function by overexpressing <i>Mfn1</i> (in OE-Mfn1 cells) and silencing <i>Mfn1</i> using short hairpin RNA (shRNA) (in shMfn1 cells). Cell proliferation capacity, mitochondrial membrane potential, and mitochondrial ATP content were measured. To investigate the effects of Mfn1 on cellular metabolism and epigenetic modifications, the levels of metabolites α-KG, A-CoA, and SAM, as well as the levels of cellular methylation and acetylation, were detected by ELISA. Differentially expressed genes and metabolites were assessed by RNA-seq and LC-MS. This study demonstrates that alterations in <i>Mfn1</i> gene expression can significantly affect mitochondrial metabolism and cell proliferation and apoptosis. In addition, Mfn1 affects the expression of genes encoding enzymes that are responsible for histone methylation and acetylation, thereby regulating these modifications. These findings provide a theoretical basis for further elucidation of the mechanisms by which Mfn1 affects cell proliferation, regulates metabolites, and modulates chromatin epigenetic modification.
ISSN:2073-4409