Session:
Building from the Bench (Model Systems to Understand Disease Mechanisms)12 April 2024, 1045 - 1215, NAK Auditorium
Presenting Title:
Deaf1 Regulates Muscle Regenaration Through Autophagy
The commonality between various muscle diseases is the loss of muscle mass, function, and regeneration, which severely restricts mobility and impairs the quality of life. With muscle stem cells (MuSCs) playing a key role in facilitating muscle repair, targeting regulators of muscle regeneration has been shown to be a promising therapeutic approach to repair muscles. However, the underlying molecular mechanisms driving muscle regeneration are complex and poorly understood. Here, we have identified a transcriptional factor, Deformed epidermal autoregulatory factor 1 (Deaf1), as a new regulator of muscle regeneration. We showed that Deaf1 targets to PI3KC3 and Atg16l1 promoter regions and suppresses their expressions, thus inhibiting autophagy. Deaf1 depletion therefore induces autophagy which blocks MuSC survival and differentiation. In contrast, Deaf1 overexpression inactivates autophagy in MuSCs, leading to increases in protein aggregates and cell death. The fact that Deaf1 depletion and overexpression both lead to defects in muscle regeneration highlights the importance of fine tuning of Deaf1-regulated autophagy during myogenesis. Significantly, we further showed that Deaf1 expression is altered in sarcopenic and cachectic MuSCs. Manipulation of Deaf1 expression can attenuate muscle atrophy and restore muscle regeneration in the mouse models of sarcopenia and cancer cachexia. Our findings together unveil a critical role for Deaf1 in muscle regeneration, providing insights into the development of uncovering new therapies against muscle atrophy.
