Restoration of cardiac mitochondrial function is related to mitochondrial dynamics efficiency and depends on the severity of endotoxemia.

ADÁN AREÁN, JUAN SANTIAGO; EVELSON, PABLO; VICO, TAMARA; ALVAREZ, SILVIA; PAPPALETTERA, BRUNO; VANASCO, VIRGINIA

Mar del Plata

Congreso; Reunión Anual de la Sociedad Argentina de Investigaciones Clínicas; 2022

Sociedad Argentina de Investigaciones Clínicas

There is a close relationship between mitochondrial ultrastructure and function.Changes in mitochondrial dynamic processes (fusion, fission, mitochondrial biogenesis, andmitophagy) could act as mechanisms leading to mitochondrial function restoration, which isaffected during endotoxemia. Our aim was to analyze if the changes in mitochondrial dynamicsare related to cardiac mitochondrial function restoration during mild and severe endotoxemia.Female Sprague Dawley rats (45 days) were ip injected with 0.5 mg/kg (low-gradeendotoxemia, LE), 8 mg/kg (severe endotoxemia, SE), or vehicle (control, C), and after 6 or 24h assays were performed in cardiac tissue. PGC1α y mTFA expression (mitochondrialbiogenesis) were increased only at 6h in LE and recovers control expression at 24h, while in SEvalues remained increased up to 24h. In LE, Parkin expression increased at 6 h while Pink1only increased at 24 h (mitophagy). In SE, both Pink1 and Parkin increased their expressionsince 6 h. TEM analysis showed mitochondrial swelling at 6 h in SE and LE. At 24h LE,mitochondrial population showed size variety and structures compatible with mitochondrialremodeling processes. Interestingly, in SE at 24h also evidence of the loss of the myofibrillarstructure and mitochondria with altered morphology is observed. To assess mitochondrialfunction recovery, ATP production and mitochondrial membrane potential were measured. InLE, ATP production was found significantly decreased (38%) at 6h, recovering control values at24h (control: 225 nmoles ATP/min mg protein, p