The mitochondrial permeability transition in liver and heart

Abstract

Abstract Opening of the inner mitochondrial membrane (IMM) permeability transition pore (PTP) dissipates ion gradients and the transmembrane electric potential (ΔΨ) across IMM, releasing excess Ca2+ from the mitochondrial matrix. Immediate closure of PTP must follow to prevent outer membrane disruption, loss of cytochrome C and eventual apoptosis. Flickering, defined as the rapid alternative opening/closing of PTP, has been reported in heart, which undergoes frequent, large variations in Ca2+. In contrast, in tissues that undergo depolarization events less frequently, such as the liver, PTP would not need to be as dynamic and thus these tissues would not be as resistant to stress. To evaluate this idea, it was decided to follow the reversibility of the permeability transition (PT) in isolated mitochondria from two different tissues: the very dynamic heart, and the liver, which suffers depolarizations less frequently. It was observed that in heart mitochondria PT remained reversible for longer periods and at higher Ca2+ loads than in liver mitochondria. This was evaluated measuring the rate of oxygen consumption, organelle swelling and Ca2+ retention capacity. It is suggested that PTP fitness varies in a tissue-specific manner.