Possible role of heme iron for mitochondrial homeostasis in the heart of Friedreich's ataxia at early stage

Autor: Yuho Kim, Varun Dhorajia, Ruiying Cheng, Jonghan Kim
Rok vydání: 2023
Předmět:
Zdroj: Physiology. 38
ISSN: 1548-9221
1548-9213
Popis: Friedreich’s ataxia (FRDA) is a rare genetic disorder that progressively develops cardiac hypertrophy and dysfunction (i.e., cardiomyopathy) along with neurodegenerative problems. Although this disease is largely caused by mitochondrial dysfunction, the underlying mechanism is unclear particularly in the heart. Using FRDA mouse model (YG8s(GAA)>800; Jackson Laboratory; #030395), we have sought to characterize the phenotype and mitochondrial markers that may be important for the development of FRDA cardiac complication. Here, we observed cardiac hypertrophy at 2-3 months old, as evidenced by increased levels of both ANP (Atrial natriuretic peptide) and BNP (Brain natriuretic peptide) in the heart of FRDA mice as compared to control mice (FXN carrier), as well as increased ratio of heart weight to body weight ( p>0.05). However, mitochondrial oxidative markers (e.g., OXPHOS, aconitase activity) were shown to be similar between FRDA and control mice, suggesting that mitochondrial function is maintained in the heart of FRDA mice at early stage. Notably, we observed that heme oxygenase-1 (HO-1) protein levels are significantly upregulated in the FRDA heart. Although increased HO-1 activity is known to elevate free iron levels, non-heme iron levels were slightly lower in the FRDA heart. Therefore, it may be possible that mitochondria can sustain their functionality in the heart of FRDA at early stage, at least in part, through altering heme iron metabolism. This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.
Databáze: OpenAIRE
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