# Inhibition of MARK4 Promotes Mitochondrial Biogenesis by Inducing the Phosphorylation of AMPKα to Reduce Myocardial Damage in Rats With Myocardial Infarction

## TL;DR

Inhibiting MARK4 in rats with heart attacks improves heart function by boosting mitochondrial production through AMPKα activation.

## Contribution

This study identifies MARK4 inhibition as a novel therapeutic target for myocardial infarction via AMPKα phosphorylation and mitochondrial biogenesis.

## Key findings

- MARK4 knockdown improved cardiac function and reduced myocardial injury in rats.
- Inhibition of MARK4 increased AMPKα phosphorylation and promoted mitochondrial biosynthesis.
- AMPKα inhibition negated mitochondrial biosynthesis effects of MARK4 knockdown.

## Abstract

Mitochondrial biogenesis is an important factor affecting the development of acute myocardial infarction. MAP/MARK4, a member of the MAP serine/threonine kinase (MARK) family, is involved in a variety of physiological processes. The aim of this study was to investigate the role of microtubule affinity‐regulating kinase 4 (MARK4) in regulating mitochondrial biogenesis in rats with myocardial infarction.

One week after the left anterior descending, coronary artery was ligated to establish a myocardial infarction model, and MARK4 expression was knocked down in mice. In the fifth week, changes in cardiac function and structure, the myocardial BNP and ATP content, mitochondrial ultrastructure, and the mitochondrial membrane potential and reactive oxygen species levels were observed and detected, and the levels of AMPKα and mitochondrial biogenesis- and apoptosis-related proteins were detected using western blot analysis.

We found that downregulating the expression of MARK4 in rats with myocardial infarction improved cardiac function, alleviated cardiac pathological injury and restored damaged mitochondrial membrane potential, effectively inhibited myocardial apoptosis and restored the myocardial energy supply, and promoted mitochondrial biosynthesis by increasing AMPKα phosphorylation. However, the addition of an AMPKα inhibitor after MARK4 knockdown did not affect mitochondrial biosynthesis in cardiomyocytes, indicating that the inhibition of MARK4 expression may be a promising therapeutic target for myocardial infarction.

Inhibition of MARK4 expression in rats with myocardial infarction plays a cardioprotective role and promotes mitochondrial biogenesis by promoting AMPKα phosphorylation.