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Adapting cytoskeleton-mitochondria patterning with myocyte differentiation by promyogenic PRR33
Xuyang Fu1,2, Feng Zhang1,2, Xiaoxuan Dong1,2
1Department of Cardiology of Second Affiliated Hospital, State Key Laboratory of Transvascular Implantation Devices, Heart Regeneration and Repair Key Laboratory of Zhejiang Province, Zhejiang University School of Medicine, Hangzhou, 310009, China.
Cell Death and Differentiation
|August 15, 2024
Summary
Researchers discovered PRR33, a novel protein crucial for muscle development. PRR33 (proline-rich protein 33) coordinates cytoskeleton and mitochondria, essential for muscle differentiation and function.
Area of Science:
- Muscle biology and cellular organization
- Skeletal muscle development and regeneration
Background:
- Coordinated cytoskeleton-mitochondria organization is vital for muscle development and function.
- The regulatory mechanisms governing this organization are not fully understood.
Purpose of the Study:
- To identify novel factors regulating cytoskeleton-mitochondria organization during myogenesis.
- To elucidate the role of PRR33 in muscle differentiation and function.
Main Methods:
- Utilized C2C12 myoblast cell line for differentiation studies.
- Generated and analyzed Prr33 knockout mouse models.
- Performed interactome and transcriptome analyses.
- Investigated protein-protein interactions using co-immunoprecipitation and microscopy.
Main Results:
- Identified PRR33 as a muscle-enriched, promyogenic factor upregulated during myogenesis.
- Prr33 depletion impaired myoblast differentiation, myofiber size, and muscle strength.
- Prr33 knockout mice showed defects in myogenesis and muscle regeneration.
- PRR33 interacts with DESMIN, regulating DESMIN-mitochondria association and mitochondrial organization.
Conclusions:
- PRR33 is a critical regulator of myogenesis and muscle function.
- PRR33 and DESMIN form a regulatory module essential for coordinating mitochondrial organization with muscle differentiation.
- Disruption of this module leads to myofiber disorganization and dysfunction.
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