# Mitochondrial cardiolipin remodeling facilitates efficient myoblast differentiation

## TL;DR

This study shows that changes in a specific mitochondrial lipid, cardiolipin, are important for efficient muscle cell differentiation.

## Contribution

The study reveals that mitochondrial cardiolipin remodeling, not MyoD, is essential for early myoblast differentiation.

## Key findings

- The proportion of linoleic acid-containing cardiolipin increases during early myoblast differentiation.
- Tafazzin expression rises with myoblast differentiation, indicating its role in cardiolipin remodeling.
- Inhibiting cardiolipin biosynthesis and remodeling suppresses differentiation, which can be partially rescued by linoleic acid.

## Abstract

During myoblast differentiation, mitochondria undergo dynamic changes in their morphology and function. Although the mitochondrial membrane lipid environment is closely related to mitochondrial integrity, how mitochondrial lipid composition changes during myoblast differentiation and whether it is involved in efficient differentiation remains unclear. In this study, we applied LC-MS/MS-based untargeted lipidomics to the mitochondria isolated from C2C12 murine myoblasts and found that the proportion of linoleic acid (C18:2)-containing cardiolipin (CL) increased during the early stages of differentiation. In parallel, the expression of tafazzin, a mitochondrial CL remodeling enzyme, increased in line with myoblast differentiation. Notably, the increase in C18:2-containing CL was not suppressed by the knockdown of MyoD (myoblast determination protein 1), a master transcription factor for myoblast differentiation. In contrast, the inhibition of CL biosynthesis and remodeling significantly suppressed differentiation progression, which was partially rescued by exogenous supplementation with C18:2. Similar trends in CL remodeling were observed when primary stem cells isolated from mouse skeletal muscle differentiated into myotubes. These results demonstrate that mitochondrial CL remodeling at an early stage is required to promote efficient myoblast differentiation.