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Updated: Jun 26, 2025
In vitro Assessment of Myocardial Protection following Hypothermia-Preconditioning in a Human Cardiac Myocytes Model
Published on: October 27, 2020
Mitochondrial outer membrane protein Samm50 protects against hypoxia-induced cardiac injury by interacting with Shmt2
Yufei Zhou1, Le Kang2, Ran Xu1
1Shanghai Institute of Cardiovascular Diseases, Department of Cardiology, Zhongshan Hospital, Fudan University, Shanghai 200032, China.
Abstract:
Cardiac remodeling is a critical process following myocardial infarction (MI), potentially leading to heart failure if untreated. The significance of mitochondrial homeostasis in MI remains insufficiently understood. Samm50 is an essential component of mitochondria. Our study aimed to investigate its role in hypoxia-induced cardiac injury and the underlying mechanisms. First, we observed that Samm50 was dynamically downregulated in mice with MI compared to the control mice. In vitro, Samm50 was also downregulated in oxygen-glucose-deprived neonatal rat cardiomyocytes and fibroblasts. Overexpression and knockdown of Samm50 mitigated and exacerbated cardiac apoptosis and fibrosis, while also improving and worsening mitochondrial homeostasis, respectively. Protein interactions with Samm50 during the protective process were identified via immune-coprecipitation/mass spectroscopy. Mechanistically, serine hydroxymethyltransferase 2 (Shmt2) interacted with Samm50, acting as a crucial element in the protective process by hindering the transfer of Bax from the cytoplasm to the mitochondria and subsequent activation of caspase-3. Inhibition of Shmt2 diminished the protective effect of Samm50 overexpression against cardiac injury. Finally, Samm50 overexpression in vivo mitigated cardiac remodeling and enhanced cardiac function in both acute and chronic MI. In conclusion, Samm50 overexpression mitigated hypoxia-induced cardiac remodeling by inhibiting apoptosis and fibrosis, with Shmt2 acting as a key regulator in this protective process. The Samm50/Shmt2 axis represents a newly discovered mitochondria-related pathway for mitigating hypoxia-induced cardiac injury.
Insights
Mitochondrial protein Samm50 protects against heart damage after myocardial infarction (MI). Samm50 overexpression, along with Shmt2, mitigates cardiac remodeling, apoptosis, and fibrosis, improving heart function.
Area of Science:
- Cardiology
- Mitochondrial Biology
- Molecular Medicine
Background:
- Cardiac remodeling post-myocardial infarction (MI) can lead to heart failure.
- The role of mitochondrial homeostasis in MI is not fully understood.
- Samm50 is a key mitochondrial protein.
Purpose of the Study:
- Investigate Samm50's role in hypoxia-induced cardiac injury.
- Elucidate the underlying protective mechanisms involving Samm50.
- Explore the Samm50/Shmt2 interaction in cardiac protection.
Main Methods:
- Studied Samm50 expression in mouse MI models and in vitro cell cultures.
- Utilized Samm50 overexpression and knockdown in cardiomyocytes and fibroblasts.
- Employed immune-coprecipitation/mass spectrometry to identify protein interactions.
- Assessed cardiac apoptosis, fibrosis, mitochondrial homeostasis, and cardiac function in vivo.
Main Results:
- Samm50 expression was downregulated in MI and hypoxia.
- Samm50 manipulation affected cardiac apoptosis, fibrosis, and mitochondrial homeostasis.
- Serine hydroxymethyltransferase 2 (Shmt2) was identified as a Samm50 interactor.
- Samm50 overexpression inhibited Bax translocation and caspase-3 activation via Shmt2.
- Samm50 overexpression improved cardiac function and reduced remodeling in MI models.
Conclusions:
- Samm50 overexpression mitigates hypoxia-induced cardiac remodeling by inhibiting apoptosis and fibrosis.
- The Samm50/Shmt2 axis is a novel mitochondrial pathway for protecting against cardiac injury.
- Targeting the Samm50/Shmt2 pathway holds therapeutic potential for MI recovery.
