A groundbreaking study titled "Loss of popdc3 Impairs Mitochondrial Function and Causes Skeletal Muscle Atrophy and Reduced Swimming Ability in Zebrafish" has been published in the Journal of Cachexia, Sarcopenia and Muscle, a prestigious JCR Q1 journal. Led by a dedicated team from Hunan Normal University, this research provides significant insights into the role of the Popeye domain containing 3 (POPDC3) protein in maintaining skeletal muscle health. Xi-Yang Peng, Xiu-Shan Wu, and Chang-Fa Tang are the co-corresponding authors of this paper, while Chen-Chen Sun is the first author.

The study reveals that the loss of popdc3 significantly impairs mitochondrial function, leading to skeletal muscle atrophy and reduced swimming ability in zebrafish. Using a combination of genetic, molecular, and physiological approaches, the researchers demonstrated that popdc3 deficiency results in decreased mitochondrial respiration and biogenesis, disrupted protein homeostasis, and ultimately, muscle wasting. These findings shed light on the underlying mechanisms of limb-girdle muscular dystrophy (LGMD) associated with POPDC3 variants.

The researchers utilized zebrafish as a model organism to investigate the effects of popdc3 deficiency. Through a series of experiments, including behavioral tests, histological analysis, transcriptome sequencing, and mitochondrial function assessments, they found that popdc3 knockout zebrafish exhibited reduced swimming ability, muscle mass, and mitochondrial respiration. These changes were accompanied by increased protein degradation and decreased protein synthesis, indicating an imbalance in protein homeostasis.

This study is the first to elucidate the molecular mechanisms by which POPDC3 variants contribute to skeletal muscle atrophy and LGMD. The findings highlight the importance of POPDC3 in maintaining mitochondrial function and skeletal muscle mass, offering potential therapeutic targets for the treatment of muscular dystrophies.