Fine-Tuning Autophagy in Skeletal Muscle: From Homeostasis to Muscle Wasting Disorders.

Area of Science:

• Cellular Biology
• Muscle Physiology
• Biochemistry

Background:

• Skeletal muscle homeostasis relies on protein turnover, organelle quality control, and metabolic adaptation.
• Impaired muscle function during aging and disease is linked to disruptions in these cellular processes.
• Autophagy, a key degradative pathway, is vital for muscle integrity, mitochondrial health, and muscle stem cell function.

Purpose of the Study:

• To review the molecular mechanisms regulating autophagy in skeletal muscle.
• To discuss the detrimental effects of both insufficient and excessive autophagy on muscle health.
• To propose a framework for understanding optimal autophagic activity in skeletal muscle.

Main Methods:

• Literature review of molecular mechanisms controlling autophagy.
• Analysis of evidence from genetic models and disease contexts.
• Discussion of nutrient-sensing pathways (AMPK, mTORC1) and transcriptional regulation.

Main Results:

• Both reduced and hyperactivated autophagy contribute to muscle atrophy and degeneration.
• Autophagy dysregulation is implicated in aging and various pathological conditions.
• A balanced autophagic flux is essential for maintaining skeletal muscle function and regeneration.

Conclusions:

• Skeletal muscle health depends on maintaining autophagic activity within a context-dependent functional range.
• Neither complete inhibition nor simple activation of autophagy is a universally beneficial therapeutic strategy.
• Understanding the optimal range of autophagy is crucial for developing effective treatments for muscle wasting disorders.