SMYD1a protects the heart from ischemic injury by regulating OPA1-mediated cristae remodeling and supercomplex formation.
Cristae
Ischemic heart failure
Methyltransferase
Mitochondrial respiration
SMYD1
Journal
Basic research in cardiology
ISSN: 1435-1803
Titre abrégé: Basic Res Cardiol
Pays: Germany
ID NLM: 0360342
Informations de publication
Date de publication:
22 05 2023
22 05 2023
Historique:
received:
26
10
2022
accepted:
10
05
2023
revised:
03
05
2023
medline:
24
5
2023
pubmed:
22
5
2023
entrez:
22
5
2023
Statut:
epublish
Résumé
SMYD1, a striated muscle-specific lysine methyltransferase, was originally shown to play a key role in embryonic cardiac development but more recently we demonstrated that loss of Smyd1 in the murine adult heart leads to cardiac hypertrophy and failure. However, the effects of SMYD1 overexpression in the heart and its molecular function in the cardiomyocyte in response to ischemic stress are unknown. In this study, we show that inducible, cardiomyocyte-specific overexpression of SMYD1a in mice protects the heart from ischemic injury as seen by a > 50% reduction in infarct size and decreased myocyte cell death. We also demonstrate that attenuated pathological remodeling is a result of enhanced mitochondrial respiration efficiency, which is driven by increased mitochondrial cristae formation and stabilization of respiratory chain supercomplexes within the cristae. These morphological changes occur concomitant with increased OPA1 expression, a known driver of cristae morphology and supercomplex formation. Together, these analyses identify OPA1 as a novel downstream target of SMYD1a whereby cardiomyocytes upregulate energy efficiency to dynamically adapt to the energy demands of the cell. In addition, these findings highlight a new epigenetic mechanism by which SMYD1a regulates mitochondrial energetics and functions to protect the heart from ischemic injury.
Identifiants
pubmed: 37212935
doi: 10.1007/s00395-023-00991-6
pii: 10.1007/s00395-023-00991-6
pmc: PMC10203008
doi:
Substances chimiques
Smyd1 protein, mouse
0
Opa1 protein, mouse
EC 3.6.1.-
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
20Subventions
Organisme : NIGMS NIH HHS
ID : R01 GM144613
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL141353
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK127979
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL165797
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK107397
Pays : United States
Informations de copyright
© 2023. The Author(s).
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