biostudies-literatureHoolachan JMAmerican Heart AssociationNIDDK NIH HHSNCI NIH HHSNIH HHSe70113https://www.ebi.ac.uk/biostudies/studies/S-EPMC12602274biostudies-literatureUnknown16(6)<h4>Background</h4>Mitochondrial homeostasis is vital for optimal skeletal muscle integrity. Mitochondrial quality control (MQC) mechanisms that are essential for maintaining proper functions of mitochondria include mitochondrial biogenesis, dynamics and mitophagy. Previously, Syntaxin 4 (STX4), traditionally considered a cell surface protein known for glucose uptake in skeletal muscle, was also identified at the outer mitochondrial membrane. STX4 enrichment was sufficient to reverse Type 2 diabetes-associated mitochondrial damage in skeletal muscle by inactivation of mitochondrial fission. However, whether STX4 could modulate skeletal muscle mitochondrial homeostasis through MQC mechanisms involving mitochondrial biogenesis or mitophagy remains to be determined.<h4>Methods</h4>To determinJournal of cachexia, sarcopenia and muscleSTX4 Is Indispensable for Mitochondrial Homeostasis in Skeletal Muscle.PMC12602274R01 DK102233DK1129712R01DK137515R01 DK137515R56 DK067912P30 CA033572DK102233R01 DK067912DK06791225CDA1454374Jiang LShirihai OHoolachan JMKiperman TPirrotte PThurmond DCMerz KEZhou CBloom-Saldana EMcCown EMHamilton AMa KOh EFueger PTBalakrishnan RfalseSTX4 Is Indispensable for Mitochondrial Homeostasis in Skeletal Muscle.<h4>Background</h4>Mitochondrial homeostasis is vital for optimal skeletal muscle integrity. Mitochondrial quality control (MQC) mechanisms that are essential for maintaining proper functions of mitochondria include mitochondrial biogenesis, dynamics and mitophagy. Previously, Syntaxin 4 (STX4), traditionally considered a cell surface protein known for glucose uptake in skeletal muscle, was also identified at the outer mitochondrial membrane. STX4 enrichment was sufficient to reverse Type 2 diabetes-associated mitochondrial damage in skeletal muscle by inactivation of mitochondrial fission. However, whether STX4 could modulate skeletal muscle mitochondrial homeostasis through MQC mechanisms involving mitochondrial biogenesis or mitophagy remains to be determined.<h4>Methods</h4>To determin2025-01-01T00:00:00Z2025 Dec2026-06-05T14:29:46.588Z2026-05-17T03:12:40.089ZS-EPMC126022744121486210.1002/jcsm.70113