Mitochondrial proteostasis mediated by CRL5Ozz and Alix maintains skeletal muscle function
Campos, Y.; Rodriguez-Enriquez, R.; Palacios, G.; Van de Vlekkert, D.; Qiu, X.; Weesner, J.; Gomero, E.; Demmers, J.; Bertorini, T.; Opferman, J. T.; Grosveld, G. T.; d'Azzo, A.
Show abstract
High energy-demanding tissues, such as skeletal muscle, require mitochondrial proteostasis to function properly. Two quality-control mechanisms, the ubiquitin proteasome system (UPS) and the release of mitochondria-derived vesicles, safeguard mitochondrial proteostasis. However, whether these processes interact is unknown. Here we show that the E3 ligase CRL5Ozz, a member of the UPS, and its substrate Alix control the mitochondrial concentration of Slc25A4, a solute carrier that is essential for ATP production. The mitochondria in Ozz-/- or Alix-/-skeletal muscle share overt morphologic alterations (they are supernumerary, swollen, and dysmorphic) and have abnormal metabolomic profiles. We found that CRL5Ozz ubiquitinates Slc25A4 and promotes its proteasomal degradation, while Alix facilitates SLC25A4 loading into exosomes destined for lysosomal destruction. The loss of Ozz or Alix offsets steady-state levels of Slc25A4, which disturbs mitochondrial metabolism and alters muscle fiber composition. These findings reveal hitherto unknown regulatory functions of Ozz and Alix in mitochondrial proteostasis.
Matching journals
The top 5 journals account for 50% of the predicted probability mass.
Similar papers in this journal
Similar papers in this journal
- The mitochondrial mRNA stabilizing protein, SLIRP, regulates skeletal muscle mitochondrial structure and respiration by exercise-recoverable mechanisms 96%
- Single-nuclei sequencing of skeletal muscle reveals subsynaptic-specific transcripts involved in neuromuscular junction maintenance 95%
- Specific heterozygous frameshift variants in hnRNPA2B1 cause early-onset oculopharyngeal muscular dystrophy 95%
Similar papers in this journal
- Mitf is a Schwann Cell Sensor of Axonal Integrity that Drives Nerve Repair 95%
- ATAD1 and the integrated stress response prevent clogging of TOM and damage caused by un-imported mitochondrial proteins 94%
- Spatially resolved transcriptomics reveals innervation-responsive functional clusters in skeletal muscle 94%
Similar papers in this journal
- AMPKα2 is a skeletal muscle stem cell intrinsic regulator of myonuclear accretion 96%
- Chondrolectin regulates the sublaminar localization and regenerative function of muscle satellite cells in mice 95%
- Role of autophagy in sepsis-induced skeletal muscle dysfunction, whole-body metabolism, and survival 94%
Similar papers in this journal
- Mitochondrial PE potentiates respiratory enzymes to amplify skeletal muscle aerobic capacity 94%
- Intravital microscopy of satellite cell dynamics and their interaction with myeloid cells during skeletal muscle regeneration 94%
- Hoxa10 mediates positional memory to govern stem cell function in adult skeletal muscle 94%
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.