First Glance at Myeloid Leukaemia Factor 2 in Cardiomyocytes

TL;DR

This study explores how MLF2, a protein linked to heart disease, may help regulate protein balance and reduce heart cell enlargement in heart failure.

Contribution

The study identifies MLF2 as a novel regulator of protein homeostasis and hypertrophic signaling in cardiomyocytes.

Findings

MLF2 is overrepresented in protein aggregates in mouse models of desmin-related cardiomyopathies.

MLF2 overexpression reduces pro-hypertrophic gene expression in cardiomyocyte models.

MLF2 interacts with αB-crystallin and is upregulated in heart failure models.

Abstract

Understanding the molecular mechanisms that maintain protein homeostasis in cardiomyocytes is fundamental for the development of causal therapies for heart failure. Chaperones, the ubiquitin–proteasome system and autophagy are major regulators of cardiac homeostasis and are crucial for cardiomyocyte function and survival. In this context, myeloid leukaemia factor 2 (MLF2) emerged as a candidate of interest, as we found it overrepresented in protein aggregates in the hearts of mouse models of desmin-related cardiomyopathies (DRM), and it has also been suggested to be associated with dilated cardiomyopathy (DCM). Here, we identified αB-crystallin (CryAB), among other proteins, as a potential interaction partner of MLF2. Functionally, MLF2 was significantly upregulated in mouse models of heart failure and in two in vitro models of cardiomyocyte hypertrophy, and its overexpression resulted in attenuation of pro-hypertrophic gene expression. Taken together, these findings provide initial evidence supporting a role for MLF2 in regulating protein homeostasis and in modulating hypertrophic signalling in cardiomyocytes.

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