Physiological evidence of mitochondrial permeability transition pore opening caused by lipid deposition leading to hepatic steatosis in db/db mice.

Free Radical Biology & Medicine
Yuan LiHui Shi

Abstract

Mitochondrial permeability transition pore (mPTP) is an important regulator in cell apoptosis and necrosis. However, its role in hepatic steatosis, especially its electrophysiological properties transformation remains elusive. Herein, using diabetes mice, we investigated the role of mPTP in hepatic steatosis triggered by diabetes and the mechanisms involved. We found that hepatic steatosis altered mitochondrial morphology, generating mega mitochondria, mitochondria swelling, calcein fluorescence quenching and mitochondrial membrane potential depolarization. At the same time, we confirmed an augmented mPTP opening with patch clamping in liver mitoplasts in db/db mice and a similar transformation with arachidonic acid (AA) simulating liquid deposition. We also found mPTP opening was significantly attenuated in wt mice after removing mitochondrial matrix, while that in db/db mice remained active. In addition, we observed that AA could directly activate mPTP in inside-out mode, independent of matrix calcium. In conclusion, we for the first time provided a physiological evidence of mPTP opening in lipid deposition, which could be directly induced by AA without Ca2+ and can be inhibited by cyclosporine A. As a result, it led to mitoc...Continue Reading

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Citations

Feb 16, 2021·Frontiers in Microbiology·Patrícia de Almeida MachadoHerbert Leonel de Matos Guedes
Apr 6, 2021·Frontiers in Endocrinology·Kamila Roszczyc-Owsiejczuk, Piotr Zabielski
Jun 23, 2021·Biological Reviews of the Cambridge Philosophical Society·Giampaolo MorcianoPaulo J Oliveira

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