Team MyoProteos (K.HNIA)

MYOPROTEOS

MyoProteos: Organelle Proteostasis in muscle cell fate and diseases

Myoproteos research program aims to decrypt functioning of proteosatsis network at the organelle level in the context of muscle cell differenciation and maintenance. We built our basic research program to address molecular and pathophysiological mechanisms of muscle atrophy in health and diseases (i.e., congenital myopathies/centronuclear myopathy) and sarcopenia (age-related muscle atrophy ). We explore anabolic cascades (PI3k, mTORC1…) and catabolic processes (ubiquitin proteasome system, autophagy) as well as epigenetic marks to identify defective proteostasis signals during muscle cell fate and maintenance. Our investigations open a route to identify and test novel therapeutic targets in congential myopathies and to decelerate muscle atrophy/dysfunction in sarcopenia/premature aging.

Team Members

Zoubida KARIM
Co-lead MyoProteos from 2027

Axe de Recherche 1

Coordinateurs:

K. HNIA & M. Vandromme

How MTM1, the missing protein in X-linked centronuclear myopathy, and its phosphoinositides susbtrates/products impact lysosome and mitochondria proteostasis.

Pathophysiological outcomes

X-linked centronuclear myopathy and sacopenic muscle.

Axe de Recherche 2

Coordinateurs:

M. Vandromme & K. HNIA

How MTM1 function could impact epigenetics/transcriptional programs during muscle cell differenciation and maintenance.

Impact physiopathologique

Altered muscle cell differenciation under physiological stress and X-linked centronuclear myopathy, XLCNM).

Axe de Recherche 3

Coordinateurs:

K. HNIA & M. Vandromme

Identify and test druggable targets to restore organelle proteostasis and/or epigenetic alterations in XLCNM mouse/cell models and to decelerate muscle atrophy and dysfunction in sarcopenic models.

publications

Articles récents

Restoration of lysosomal membrane integrity in cell models of Pompe disease depends on fatty acid synthase and its product palmitic acid. Le Guillou E, Segaloni A, Gadault A, Oliveira Dias C, Henneman NF, Su M, Nemazanyy I, Hifdi N, Nivet-Antoine V, Laemmerhofer M, Hnia K, Caillaud C, Panasyuk G. Cell Mol Biol Lett. 2026 Apr 9. doi: 10.1186/s11658-026-00897-w. https://pubmed.ncbi.nlm.nih.gov/41957585/

Lysosomal phosphoinositide turnover acts upstream of RagGTPase-mTORC1 and controls muscle growth. Picot M, Hifdi N, Vaucourt M, Mansat M, Li P, Singer I, Chicanne G, Stella A, Kuang S, Miceli C, Henneman NF, Payrastre B, Vandromme M, Schiltz O, Nemazanyy I, de Araujo MEG, Panasyuk G, Viaud J, Lämmerhofer M, Hnia K. Nat Metab. 2026 Mar;8(3):624-645. doi: 10.1038/s42255-026-01484-1. https://pubmed.ncbi.nlm.nih.gov/41851531/

Mansat M, Kpotor AO, Chicanne G, Picot M, Mazars A, Flores-Flores R, Payrastre B, Hnia K, Viaud J. MTM1-mediated production of phosphatidylinositol 5-phosphate fuels the formation of podosome-like protrusions regulating myoblast fusion. Proc Natl Acad Sci U S A. 2024 Jun 4;121(23): e2217971121. PMID: 38805272. https://pubmed.ncbi.nlm.nih.gov/38805272/

Alkhoury C, Henneman NF, Petrenko V, Shibayama Y, Segaloni A, Gadault A, Nemazanyy I, Le Guillou E, Wolide AD, Antoniadou K, Tong X, Tamaru T, Ozawa T, Girard M, Hnia K, Lutter D, Dibner C, Panasyuk G. Class 3 PI3K coactivates the circadian clock to promote rhythmic de novo purine synthesis. Nat Cell Biol. 2023 Jul;25(7):975-988. PMID: 37414850. https://pubmed.ncbi.nlm.nih.gov/37414850/

Gaillard S, Charasson V, Ribeyre C, Salifou K, Pillaire MJ, Hoffmann JS, Constantinou A, Trouche D, Vandromme M. KDM5A and KDM5B histone-demethylases contribute to HU-induced replication stress response and tolerance. Biol Open. 2021 May 15;10(5):bio057729. PMID: 34184733. https://pubmed.ncbi.nlm.nih.gov/34184733/

Anquetil T, Solinhac R, Jaffre A, Chicanne G, Viaud J, Darcourt J, Orset C, Geuss E, Kleinschnitz C, Vanhaesebroeck B, Vivien D, Hnia K, Larrue V, Payrastre B, Gratacap MP. PI3KC2β inactivation stabilizes VE-cadherin junctions and preserves vascular integrity. EMBO Rep. 2021 Jun 4;22(6):e51299. PMID: 33880878. https://pubmed.ncbi.nlm.nih.gov/34184733/

Gavriilidis C, Laredj L, Solinhac R, Messaddeq N, Viaud J, Laporte J, Sumara I, Hnia K. The MTM1-UBQLN2-HSP complex mediates degradation of misfolded intermediate filaments in skeletal muscle. Nat Cell Biol. 2018 Feb;20(2):198-210. Epub 2018 Jan 22. PMID: 29358706. https://pubmed.ncbi.nlm.nih.gov/29358706/

Revues récentes

Nesrine Hifdi, Mathilde Vaucourt, Karim Hnia, Ganna Panasyuk, Marie Vandromme. Phosphoinositide signaling in the nucleus: impacts on chromatin and transcription regulation. Biology of the Cell, 2025 (In Press).

Shaping Striated Muscles with Ubiquitin Proteasome System in Health and Disease.
Hnia K, Clausen T, Moog-Lutz C. Trends Mol Med. 2019 Sep;25(9):760-774. https://pubmed.ncbi.nlm.nih.gov/31235369/

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