Loss of function of phosphatidylserine synthase causes muscle atrophy in Drosophila

• Published in: Developmental biology Vol. 511; pp. 1 - 11
• Main Authors: Kim, Sangseob, Heo, Hyun, Kwon, Seung-Hae, Park, Jae H., Lee, Gyunghee, Jeon, Sang-Hak
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.07.2024
• Subjects: Akt/FoxO; Animals; Apoptosis; Autophagy; Autophagy - genetics; Drosophila - metabolism; Drosophila melanogaster; Drosophila Proteins - genetics; Drosophila Proteins - metabolism; Forkhead Transcription Factors - genetics; Forkhead Transcription Factors - metabolism; Gene Knockdown Techniques; Mitochondria; Mitochondria - metabolism; Mitochondria - pathology; Muscle atrophy; Muscle, Skeletal - metabolism; Muscle, Skeletal - pathology; Muscular Atrophy - metabolism; Muscular Atrophy - pathology; Phosphatidylserine synthase; Proto-Oncogene Proteins c-akt - genetics; Proto-Oncogene Proteins c-akt - metabolism; Reactive Oxygen Species - metabolism; Sarcopenia; Sarcopenia - metabolism; Sarcopenia - pathology; Sarcopenia; Phosphatidylserine synthase; Muscle atrophy; Mitochondria; Akt/FoxO; Autophagy
• ISSN: 0012-1606; 1095-564X
• DOI: 10.1016/j.ydbio.2024.03.006

Maintenance of appropriate muscle mass is crucial for physical activity and metabolism. Aging and various pathological conditions can cause sarcopenia, a condition characterized by muscle mass decline. Although sarcopenia has been actively studied, the mechanisms underlying muscle atrophy are not well understood. Thus, we aimed to investigate the role of Phosphatidylserine synthase (Pss) in muscle development and homeostasis in Drosophila. The results showed that muscle-specific Pss knockdown decreased exercise capacity and produced sarcopenic phenotypes. In addition, it increased the apoptosis rate because of the elevated reactive oxygen species production resulting from mitochondrial dysfunction. Moreover, the autophagy rate increased due to increased FoxO activity caused by reduced Akt activity. Collectively, these findings demonstrate that enhanced apoptosis and autophagy rates resulting from muscle-specific Pss knockdown jointly contribute to sarcopenia development, highlighting the key role of the PSS pathway in muscle health. [Display omitted] •Phosphatidylserine synthase (Pss) crucially influences muscle health in Drosophila.•Muscle-specific Pss knockdown enhances the apoptosis and autophagy rate.•Muscle-specific Pss knockdown induces sarcopenic phenotypes in Drosophila.