Mitochondrial Oxidative Stress Mediates Bradyarrhythmia in Leigh Syndrome Mitochondrial Disease Mice.

Chen B, Daneshgar N, Lee HC, Song LS, Dai DF

Antioxidants (Basel, Switzerland)26 Apr 2023Cited by 11 (Europe PMC)

PMID37237867PMCIDPMC10215409DOI10.3390/antiox12051001PepBankPUB-37237867

Summary

Mitochondrial oxidative stress has been implicated in aging and several cardiovascular diseases, including heart failure and cardiomyopathy, ventricular tachycardia, and atrial fibrillation. The role of mitochondrial oxidative stress in bradyarrhythmia is less clear. Mice with a germline deletion of Ndufs4 subunit respiratory complex I develop severe mitochondrial encephalomyopathy resembling Leigh Syndrome (LS). Several types of cardiac bradyarrhythmia are present in LS mice, including a frequent sinus node dysfunction and episodic atrioventricular (AV) block. Treatment with the mitochondrial antioxidant Mitotempo or mitochondrial protective peptide SS31 significantly ameliorated the bradyarrhythmia and extended the lifespan of LS mice. Using an ex vivo Langendorff perfused heart with live confocal imaging of mitochondrial and total cellular reactive oxygen species (ROS), we showed increased ROS in the LS heart, which was potentiated by ischemia-reperfusion. A simultaneous ECG recording showed a sinus node dysfunction and AV block concurrent with the severity of the oxidative stress. Treatment with Mitotempo abolished ROS and restored the sinus rhythm. Our study reveals robust evidence of the direct mechanistic roles of mitochondrial and total ROS in bradyarrhythmia in the setting of LS mitochondrial cardiomyopathy. Our study also supports the potential clinical application of mitochondrial-targeted antioxidants or SS31 for the treatment of LS patients.

CC BYText from Europe PMC. Highlighted sentences are the source of results.

Results from this study2

No result from this study comes from a test of the peptide.

Studies that did not test the peptide alone2

In this study, Elamipretide (SS-31) was a lab tool or a carrier, part of a mix, or the subject of a lab method. These results are not evidence about taking Elamipretide (SS-31).

01AnimalNot a test of Elamipretide (SS-31) aloneAnimal study (in vivo)Efficacy outcome
In Leigh Syndrome mice, treatment with Mitotempo or SS31 (reported together) significantly ameliorated bradyarrhythmia.
In plain wordsIn mice with Leigh Syndrome, treatment with Mitotempo or SS31, reported together, reduced slow heart rhythm problems.
Peptide
Elamipretide (SS-31)
Outcome
DecreaseBradyarrhythmia
Study
mousen: not reported in source
Ndufs4 knockout Leigh Syndrome mice
Outcome group
Heart function · Cardiovascular
Source sentences
Summary
Treatment with the mitochondrial antioxidant Mitotempo or mitochondrial protective peptide SS31 significantly ameliorated the bradyarrhythmia
1 context sentence(design, population, supporting numbers)
Summary · context
Mice with a germline deletion of Ndufs4 subunit respiratory complex I develop severe mitochondrial encephalomyopathy resembling Leigh Syndrome (LS).
In this study, Elamipretide (SS-31) was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Elamipretide (SS-31).
Show in the study text Report a problemFND-3723786701
02AnimalNot a test of Elamipretide (SS-31) aloneAnimal study (in vivo)Efficacy outcome
In Leigh Syndrome mice, treatment with Mitotempo or SS31 (reported together) extended lifespan.
In plain wordsIn mice with Leigh Syndrome, treatment with Mitotempo or SS31, reported together, lengthened life.
Peptide
Elamipretide (SS-31)
Outcome
IncreaseLifespan
Study
mousen: not reported in source
Ndufs4 knockout Leigh Syndrome mice
Outcome group
Mortality · Whole body
Source sentences
Summary
Treatment with the mitochondrial antioxidant Mitotempo or mitochondrial protective peptide SS31 significantly ameliorated the bradyarrhythmia and extended the lifespan of LS mice
1 context sentence(design, population, supporting numbers)
Summary · context
Mice with a germline deletion of Ndufs4 subunit respiratory complex I develop severe mitochondrial encephalomyopathy resembling Leigh Syndrome (LS).
In this study, Elamipretide (SS-31) was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Elamipretide (SS-31).
Show in the study text Report a problemFND-3723786702

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Version history

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Version 2Current
10 Oct 2026, 08:19 UTC
Study results updated
Version 1
9 Oct 2026, 02:47 UTC
First added · source update from Europe PMC

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