PMID- 33178040 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20201113 IS - 1664-042X (Print) IS - 1664-042X (Electronic) IS - 1664-042X (Linking) VI - 11 DP - 2020 TI - Palmitoyl Protein Thioesterase 1 Is Essential for Myogenic Autophagy of C2C12 Skeletal Myoblast. PG - 569221 LID - 10.3389/fphys.2020.569221 [doi] LID - 569221 AB - Skeletal muscle differentiation is an essential process for the maintenance of muscle development and homeostasis. Reactive oxygen species (ROS) are critical signaling molecules involved in muscle differentiation. Palmitoyl protein thioesterase 1 (PPT1), a lysosomal enzyme, is involved in removing thioester-linked fatty acid groups from modified cysteine residues in proteins. However, the role of PPT1 in muscle differentiation remains to be elucidated. Here, we found that PPT1 plays a critical role in the differentiation of C2C12 skeletal myoblasts. The expression of PPT1 gradually increased in response to mitochondrial ROS (mtROS) during muscle differentiation, which was attenuated by treatment with antioxidants. Moreover, we revealed that PPT1 transactivation occurs through nuclear factor erythroid 2-regulated factor 2 (Nrf2) binding the antioxidant response element (ARE) in its promoter region. Knockdown of PPT1 with specific small interference RNA (siRNA) disrupted lysosomal function by increasing its pH. Subsequently, it caused excessive accumulation of autophagy flux, thereby impairing muscle fiber formation. In conclusion, we suggest that PPT1 is factor a responsible for myogenic autophagy in differentiating C2C12 myoblasts. CI - Copyright (c) 2020 Yun, Jo, Kim, Nguyen, Shin, Kim and Choi. FAU - Yun, Hyeong Rok AU - Yun HR AD - Department of Biomedical Science, Graduate School, Kyung Hee University, Seoul, South Korea. AD - Biomedical Science Institute, Kyung Hee University, Seoul, South Korea. FAU - Jo, Yong Hwa AU - Jo YH AD - Biomedical Science Institute, Kyung Hee University, Seoul, South Korea. AD - Department of Biochemistry and Molecular Biology, School of Medicine, Kyung Hee University, Seoul, South Korea. FAU - Kim, Jieun AU - Kim J AD - Biomedical Science Institute, Kyung Hee University, Seoul, South Korea. AD - Department of Biochemistry and Molecular Biology, School of Medicine, Kyung Hee University, Seoul, South Korea. FAU - Nguyen, Ngoc Ngo Yen AU - Nguyen NNY AD - Biomedical Science Institute, Kyung Hee University, Seoul, South Korea. AD - Department of Biochemistry and Molecular Biology, School of Medicine, Kyung Hee University, Seoul, South Korea. FAU - Shin, Yoonhwa AU - Shin Y AD - Department of Biomedical Science, Graduate School, Kyung Hee University, Seoul, South Korea. AD - Biomedical Science Institute, Kyung Hee University, Seoul, South Korea. FAU - Kim, Sung Soo AU - Kim SS AD - Biomedical Science Institute, Kyung Hee University, Seoul, South Korea. AD - Department of Biochemistry and Molecular Biology, School of Medicine, Kyung Hee University, Seoul, South Korea. FAU - Choi, Tae Gyu AU - Choi TG AD - Biomedical Science Institute, Kyung Hee University, Seoul, South Korea. AD - Department of Biochemistry and Molecular Biology, School of Medicine, Kyung Hee University, Seoul, South Korea. LA - eng PT - Journal Article DEP - 20201015 PL - Switzerland TA - Front Physiol JT - Frontiers in physiology JID - 101549006 PMC - PMC7593845 OTO - NOTNLM OT - autophagy OT - mammalian target of rapamycin complex OT - mitochondrial reactive oxygen species OT - muscle differentiation OT - palmitoyl protein thioesterase 1 EDAT- 2020/11/13 06:00 MHDA- 2020/11/13 06:01 PMCR- 2020/10/15 CRDT- 2020/11/12 05:42 PHST- 2020/06/03 00:00 [received] PHST- 2020/09/10 00:00 [accepted] PHST- 2020/11/12 05:42 [entrez] PHST- 2020/11/13 06:00 [pubmed] PHST- 2020/11/13 06:01 [medline] PHST- 2020/10/15 00:00 [pmc-release] AID - 10.3389/fphys.2020.569221 [doi] PST - epublish SO - Front Physiol. 2020 Oct 15;11:569221. doi: 10.3389/fphys.2020.569221. eCollection 2020.