replika saat paykwik erotik film izle pvc yer kaplamasi tanitim filmi protez sac c99 shell ankara escort izmir escort cialis fiyat cialis klima servisi betboo youwin dusuk hapi film izle yabanci dizi izle istanbul bocek ilaclama youwin giris ngsbahis giris
CHANNEL FORMATION BY MITOCHONDRIAL ATP SYNTHASES. REGULATION BY Ca2+ AND OXIDATIVE STRESS

CHANNEL FORMATION BY MITOCHONDRIAL ATP SYNTHASES. REGULATION BY Ca2+ AND OXIDATIVE STRESS

Paolo BERNARDI

(Padova, Italy)

CHANNEL FORMATION BY MITOCHONDRIAL ATP SYNTHASES. REGULATION BY Ca2+ AND OXIDATIVE STRESS

03:30 PM 20 April / Nisan 2018

Abstract

Mitochondria can undergo an increase of inner membrane permeability (the permeability transition, PT) causing inner membrane depolarization, Ca2+ release and cessation of ATP synthesis. Prolonged openings may cause matrix swelling and outer membrane rupture with release of intermembrame proteins. The PT requires matrix Ca2+, is favored by oxidative stress and inhibited by matrix H+ and Mg2+/ATP(ADP). The PT is mediated by opening of a high-conductance channel, the PT pore (PTP) or mitochondrial megachannel (MMC) [1]. Cyclophilin D (CyPD) is the best characterized protein modulator of the PTP and the receptor for its inhibitor cyclosporin A (CsA). The pursuit of the PTP has taken a new course after the discovery that CyPD interacts with, and modulates, the F1FO (F)-ATP synthase as well [2]. The subsequent demonstration that bovine, human, yeast and drosophila F-ATP synthases form Ca2+-activated channels set the foundation for the hypothesis that the PTP originates from specific conformations of F-ATP synthase [3]. The debate is open as to whether and how F-ATP synthase can undergo a transition from key energy-conserving enzyme to energydissipating channel that favors or causes cell death. We will discuss recent advances in this rapidly moving field based on site-directed mutagenesis of selected residues of F-ATP synthase.

1. Bernardi P, Rasola A, Forte M & Lippe G (2015) The Mitochondrial Permeability Transition Pore: Channel Formation by F-ATP Synthase, Integration in Signal Transduction, and Role in Pathophysiology. Physiol Rev 95, 1111-1155.

2. Giorgio V, Bisetto E, Soriano ME, Dabbeni-Sala F, Basso E, Petronilli V, Forte MA, Bernardi P & Lippe G (2009) Cyclophilin D modulates mitochondrial F0F1-ATP synthase by interacting with the lateral stalk of the complex. J Biol Chem 284, 3398233988.

3. Bernardi P & Lippe G (2017) Channel Formation by F-ATP Synthase and the Permeability Transition Pore: An Update. Curr Opin Physiol, in press.