Study summary · research use only
MOTS-c attenuates cardiac dysfunction following high altitude exposure by promoting mitophagy
Plain-language summary
Paraphrased from the published abstract below — not a verdict on whether anything works.
In this study (mice exposed to simulated high-altitude in a decompression chamber; also includes human patients with high-altitude heart disease and acute coronary syndrome), the authors examined cardiac changes after high-altitude exposure and de-acclimatization. Mice were exposed to a simulated 6000-m altitude for 10 days, followed by 10 days at 400 m. Cardiac dysfunction persisted through de-acclimatization, alongside mitochondrial dysfunction and reduced levels of the peptide MOTS-c. Exogenous MOTS-c supplementation during de-acclimatization was associated with reduced cardiac dysfunction, reportedly through activation of the Pink1/Parkin pathway and increased mitophagy; silencing Pink1 removed this association. Circulating MOTS-c was reported to be lower in patients with high-altitude heart disease and acute coronary syndrome. The authors describe MOTS-c deficiency as linked to a lasting memory of cardiac dysfunction after high-altitude exposure.
Abstract
Prolonged exposure to high altitude (HA) results in a range of systemic changes, some of which, specifically for the heart, particularly cardiac changes, remain difficult to reverse after returning to low altitude. Cardiac de-acclimatization after HA exposure and its underlying mechanisms remain unclear. In this study, mice were subjected to a decompression chamber to simulate a 6000-m altitude exposure for 10 days, followed by the other 10-day de-acclimatization period at a lower altitude of 400 m. The cardiac dysfunction induced by HA exposure persisted throughout the de-acclimatization, accompanied with sustained mitochondrial dysfunction and the short peptide mitochondrial open reading frame of the 12S ribosomal RNA type-c (MOTS-c) deficiency. Exogenous supplementation of MOTS-c during de-acclimatization effectively alleviated the cardiac dysfunction post HA exposure. Mechanistically, MOTS-c activated the PTEN-induced putative kinase 1 (Pink1)/Parkin pathway, promoting mitophagy and improving mitochondrial quality. Silencing Pink1 abolished the protective effects of MOTS-c during de-acclimatization. Additionally, reduced circulating MOTS-c levels were observed in patients with high altitude heart disease and acute coronary syndrome. These results suggest that HA exposure leaves a memory of cardiac dysfunction upon return to lower altitude. This is attributed to a sustained deficiency in MOTS-c. MOTS-c maintains mitochondrial quality through promoting mitophagy, highlighting its therapeutic potential for treating HA-induced cardiac dysfunction during de-acclimatization.
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