Physiological aspects of the mitochondrial cyclosporin A-insensitive palmitate/Ca2+-induced pore: tissue specificity, age profile and dependence on the animal's adaptation to hypoxia.
Earlier we found that being added to rat liver mitochondria, palmitic acid (Pal) plus Ca(2+) opened a cyclosporin A-insensitive pore, which remained open for a short time. Apparently, this pore is involved in the Pal-induced apoptosis and may also take part in the mitochondrial Ca(2+) recycling as a Ca(2+) efflux system (Belosludtsev et al. J Bioenerg Biomembr 38:113-120, 2006; Mironova et al. J. Bioenerg. Biomembr. 39:167-174, 2007). In this paper, we continue studying physiological and regulatory aspects of the pore. The following observations have been made. (1) Cardiolipin has been found to facilitate the Ca(2+)-induced formation of pores in the Pal-containing liposomal membranes. (2) The opening of Pal/Ca(2+)-induced pore is accompanied by the release of apoptosis-induced factor (AIF) from mitochondria. (3) The rate of Pal/Ca(2+)-induced swelling of rat liver mitochondria increases substantially with the age of animals. (4) Although the Pal/Ca(2+)-induced pore opens both in the liver and heart mitochondria, the latter require higher Pal concentrations for the pore to open. (5) The pore opening depends on the resistance of animals to hypoxia: in the highly resistant to hypoxia rats, the mitochondrial Pal/Ca(2+)-induced pore opens easier than in the low resistant animals, this being opposite for the classical, cyclosporin A-sensitive MPT pore. The adaptation of the low resistant rats to oxygen deficiency increases the sensitivity of their mitochondria to PalCaP inductors. The paper also discusses a possible role of the mitochondrial Pal/Ca(2+)-induced pore in the protection of tissues against hypoxia.
Belosludtsev
Konstantin N
KN
Institute of Theoretical and Experimental Biophysics RAS, Pushchino, Moscow Region, 142290, Russia.
Saris
Nils-Erik L
NE
Belosludtseva
Natalia V
NV
Trudovishnikov
Alexander S
AS
Lukyanova
Lyudmila D
LD
Mironova
Galina D
GD
D000222:Adaptation, Physiological / Q000187:drug effects; D000375:Aging / Q000187:drug effects / Q000378:metabolism*; D000818:Animals; D002118:Calcium / Q000008:administration & dosage*; D002478:Cells, Cultured; D016572:Cyclosporine / Q000378:metabolism*; D000860:Hypoxia / Q000503:physiopathology*; D007113:Immunity, Innate; D015640:Ion Channel Gating / Q000187:drug effects*; D008930:Mitochondria, Liver / Q000187:drug effects / Q000378:metabolism*; D009928:Organ Specificity; D019308:Palmitic Acid / Q000008:administration & dosage*; D016062:Porosity / Q000187:drug effects; D051381:Rats
D019308:Palmitic Acid; D016572:Cyclosporine; D002118:Calcium
Biochim Biophys Acta. 1969 Jan 14;172(1):52-65
4387597
Biochim Biophys Acta. 2006 Feb;1762(2):148-63
16324828
Eur J Biochem. 1992 Oct 1;209(1):267-73
1396703
J Bioenerg Biomembr. 2007 Apr;39(2):167-74
17530392
Biofizika. 2009 May-Jun;54(3):464-70
19569507
Biochim Biophys Acta. 1985 Jun 12;822(1):1-42
2408671
Mol Cell Biochem. 1993 Jun 9-23;123(1-2):175-84
8232261
J Bioenerg Biomembr. 2006 Apr;38(2):113-20
16847595
Biochem J. 2005 Jan 15;385(Pt 2):445-50
15294016
Arch Biochem Biophys. 2001 Feb 1;386(1):52-61
11361000
Proc Natl Acad Sci U S A. 1997 Apr 1;94(7):3064-9
9096346
J Bioenerg Biomembr. 2004 Apr;36(2):171-8
15224966
Biochim Biophys Acta. 1998 Feb 25;1363(2):100-24
9507078
J Membr Biol. 2007 Jan;215(1):57-68
17443385
Nat Med. 2003 Aug;9(8):1062-8
12858170
Circulation. 2004 Aug 3;110(5):528-33
15262832
J Bioenerg Biomembr. 2001 Aug;33(4):319-31
11710807
Cell Death Differ. 2005 Feb;12(2):162-76
15592434
Arch Biochem Biophys. 2001 Feb 1;386(1):37-51
11360999
Endocrinology. 2003 Nov;144(11):5014-21
12960023
Int J Clin Pract Suppl. 2004 Oct;(143):9-21
16035392
Vestn Ross Akad Med Nauk. 1995;(10):48-55
8601092
J Neurochem. 2003 Feb;84(4):655-68
12562510
FEBS Lett. 1997 Oct 13;416(1):15-8
9369223
J Bioenerg Biomembr. 2007 Aug;39(4):313-20
17917798
FEBS Lett. 1998 Feb 27;423(3):275-80
9515723
Biochemistry (Mosc). 2005 Jul;70(7):815-21
16097947
Biochim Biophys Acta. 2004 Oct 4;1658(3):187-94
15450956
Exp Gerontol. 2006 Jul;41(7):697-703
16621391
Biochim Biophys Acta. 2003 Sep 30;1606(1-3):1-21
14507424
Free Radic Biol Med. 2005 Jan 1;38(1):12-23
15589367
Am J Physiol Heart Circ Physiol. 2000 Nov;279(5):H2124-32
11045945
J Lipid Res. 1967 May;8(3):170-80
4292227
J Biol Chem. 1951 Nov;193(1):265-75
14907713
Arch Biochem Biophys. 1989 Sep;273(2):466-78
2774563