Heart mitochondrial dynamics, bioenergetics and structure: interrelated mechanisms in acute endotoxemia.

ADÁN AREÁN, JUAN SANTIAGO; PAPPALETTERA, BRUNO; EVELSON, PABLO; VICO, TAMARA; MARCHINI, TIMOTEO; VANASCO, VIRGINIA; RUKAVINA-MIKUSIC, IVANA A; VALDEZ, LAURA; ALVAREZ, SILVIA

Siena

Congreso; The Future of Redox Biology; 2022

This work is aimed to elucidate mitochondrial dynamics as a fundamental effector of cardiac tissue energy management in endotoxemia. Female Sprague-Dawley rats were subjected to low-grade endotoxemia (LPS ip injection 0.5 mg kg -1 body weight) and severe endotoxemia (LPS ip injection 8 mg kg -1 body weight) for 6 or 24 h. TEM analysis after 6 h for both LPS doses showed structures compatible with damaged mitochondria. In severe endotoxemia, highly damaged mitochondrial structures were observed, being these results associated with a 20% decrease in mitochondrial inner membrane potential and low ATP production rates. Expression of proteins involved in mitochondrial fusion/fission (OPA-1 / DRP-1), biogenesis (PGC-1ɑ / mtTFA) and mitophagy (Pink1), were studied. Low-grade endotoxemia exhibited an increase in DRP-1 and Pink1 expression at 6 or 24h respectively. Severe endotoxemia showed increased Pink-1 expression after 6 and 24 h treatment. Both treatments showed increased levels of PGC-1ɑ and mtTFA at 6 and 24 h. The observed results suggest that the severity of endotoxemia relates to the degree of mitochondrial dysfunction and structural damage, and is linked to changes in mitochondrial dynamics. These novel results contribute to the future of therapeutics aimed to preserve this organ from inflammatory and oxidativedamage.