Mitochondria in cardiomyocyte Ca2+ signaling.
Ca(2+) signaling is of vital importance to cardiac cell function and plays an important role in heart failure. It is based on sarcolemmal, sarcoplasmic reticulum and mitochondrial Ca(2+) cycling. While the first two are well characterized, the latter remains unclear, controversial and technically challenging. In mammalian cardiac myocytes, Ca(2+) influx through L-type calcium channels in the sarcolemmal membrane triggers Ca(2+) release from the nearby junctional sarcoplasmic reticulum to produce Ca(2+) sparks. When this triggering is synchronized by the cardiac action potential, a global [Ca(2+)](i) transient arises from coordinated Ca(2+) release events. The ends of intermyofibrillar mitochondria are located within 20 nm of the junctional sarcoplasmic reticulum and thereby experience a high local [Ca(2+)] during the Ca(2+) release process. Both local and global Ca(2+) signals may thus influence calcium signaling in mitochondria and, reciprocally, mitochondria may contribute to the local control of calcium signaling. In addition to the intermyofibrillar mitochondria, morphologically distinct mitochondria are also located in the perinuclear and subsarcolemmal regions of the cardiomyocyte and thus experience a different local [Ca(2+)]. Here we review the literature in regard to several issues of broad interest: (1) the ultrastructural basis for mitochondrion - sarcoplasmic reticulum cross-signaling; (2) mechanisms of sarcoplasmic reticulum signaling; (3) mitochondrial calcium signaling; and (4) the possible interplay of calcium signaling between the sarcoplasmic reticulum and adjacent mitochondria. Finally, this review discusses experimental findings and mathematical models of cardiac calcium signaling between the sarcoplasmic reticulum and mitochondria, identifies weaknesses in these models, and suggests strategies and approaches for future investigations.
Lukyanenko
Valeriy
V
Medical Biotechnology Center, University of Maryland Biotechnology Institute, Baltimore, MD 21201, USA. lukyanen@umbi.umd.edu
Chikando
Aristide
A
Lederer
W J
WJ
D000818:Animals; D020013:Calcium Signaling / Q000502:physiology*; D006801:Humans; D008929:Mitochondria, Heart / Q000378:metabolism*; D008954:Models, Biological; D032383:Myocytes, Cardiac / Q000378:metabolism*; D012519:Sarcoplasmic Reticulum / Q000378:metabolism
Am J Physiol Cell Physiol. 2000 Apr;278(4):C747-64
10751324
Cell Calcium. 2000 Nov-Dec;28(5-6):339-48
11115373
Nature. 2008 Dec 4;456(7222):605-10
19052620
Nature. 2001 Mar 29;410(6828):592-6
11279498
Cardiovasc Res. 1999 Jan;41(1):135-46
10325961
Nature. 2004 Jan 22;427(6972):360-4
14737170
Science. 1995 May 19;268(5213):1042-5
7754383
J Neurochem. 1996 Jan;66(1):403-11
8522981
Biochim Biophys Acta. 1980 Jul 8;591(2):251-65
7397124
J Mol Cell Cardiol. 2002 Aug;34(8):951-69
12234765
J Mol Cell Cardiol. 1998 Oct;30(10):1929-37
9799647
Cardiovasc Res. 1999 Apr;42(1):254-61
10435018
J Cardiovasc Electrophysiol. 2002 Jan;13(1):88-91
11843491
Physiol Rev. 1999 Jul;79(3):917-1017
10390520
Annu Rev Physiol. 2007;69:19-49
17059356
Proc Natl Acad Sci U S A. 2007 Sep 18;104(38):14958-63
17848521
Biochemistry. 2006 Feb 28;45(8):2524-36
16489745
J Gen Physiol. 1985 Feb;85(2):291-320
2580044
Arch Biochem Biophys. 1985 Aug 1;240(2):723-33
2411223
Cell Calcium. 2001 Jul;30(1):19-27
11396984
Science. 1995 May 19;268(5213):1045-9
7754384
Prog Biophys Mol Biol. 2004 Jun-Jul;85(2-3):279-99
15142748
J Physiol. 1997 Apr 15;500 ( Pt 2):297-309
9147318
Cardiovasc Res. 1992 Mar;26(3):193-214
1423412
Physiol Rev. 2007 Jan;87(1):99-163
17237344
Arch Surg. 1985 Mar;120(3):332-8
2982344
J Theor Biol. 1979 Aug 21;79(4):491-541
159983
Biophys J. 1994 Nov;67(5):1942-56
7858131
Mol Cell Biochem. 1994 Jan 26;130(2):159-71
8028595
Br J Pharmacol. 1999 Aug;127(8):1846-50
10482915
EMBO J. 2001 Sep 3;20(17):4998-5007
11532963
Nanomedicine (Lond). 2007 Dec;2(6):831-46
18095849
J Physiol. 1998 Mar 15;507 ( Pt 3):667-77
9508828
Biophys J. 2003 Apr;84(4):2734-55
12668482
Annu Rev Physiol. 2007;69:51-67
17007587
J Physiol. 1993 Jan;460:603-21
8387590
J Mol Cell Cardiol. 1999 Nov;31(11):2063-76
10591032
Biophys J. 2002 Dec;83(6):2918-45
12496068
J Surg Res. 1986 May;40(5):495-8
3736033
Biophys J. 2004 Nov;87(5):3351-71
15347581
Cell Calcium. 1993 Mar;14(3):185-200
8500135
Circ Res. 2006 Aug 4;99(3):283-91
16794184
Proc R Soc Lond B Biol Sci. 1984 Dec 22;223(1231):223-38
6151661
Biophys Chem. 2007 Sep;129(2-3):93-110
17566629
J Cell Biol. 1988 Aug;107(2):481-95
3417757
Biophys J. 2001 Aug;81(2):785-98
11463625
Biophys J. 2008 Sep;95(5):2583-98
18424491
J Physiol. 2000 Dec 15;529 Pt 3:553-64
11118489
J Physiol. 2003 Mar 1;547(Pt 2):453-62
12562922
Mol Cell Biochem. 2008 Nov;318(1-2):147-65
18629616
J Biol Chem. 2003 May 23;278(21):19062-70
12660243
J Cell Biol. 1993 Feb;120(4):969-80
8381786
Biophys J. 2006 Jan 1;90(1):77-91
16214852
J Physiol. 2007 Aug 15;583(Pt 1):251-69
17627991
Am J Physiol. 1996 Jan;270(1 Pt 1):C148-59
8772440
J Physiol. 1999 Dec 15;521 Pt 3:575-85
10601490
Proc Natl Acad Sci U S A. 2008 Dec 2;105(48):18746-51
19033201
Biophys J. 1992 Aug;63(2):497-517
1330031
Proc Natl Acad Sci U S A. 2008 Feb 12;105(6):2198-202
18268335
EMBO J. 2001 Aug 1;20(15):4107-21
11483514
J Cardiovasc Pharmacol. 1993 Apr;21(4):595-9
7681905
J Cell Biol. 1968 May;37(2):345-69
5656397
Arch Mal Coeur Vaiss. 1999 Apr;92 Spec No 1:9-16
10326153
Anat Rec. 1981 Jun;200(2):139-51
7270916
Jpn Heart J. 1996 Jan;37(1):1-17
8632617
FASEB J. 1998 Nov;12(14):1507-20
9806760
Biophys J. 2000 Jul;79(1):39-50
10866936
Am J Physiol. 1999 Mar;276(3):H865-72
10070069
Biochem Biophys Res Commun. 1978 Sep 29;84(2):482-8
214079
J Biol Chem. 1999 Feb 26;274(9):5654-8
10026183
J Clin Invest. 2008 Jun;118(6):2230-45
18483626
Biochem J. 1999 Jul 15;341 ( Pt 2):233-49
10393078
Arch Biochem Biophys. 1999 Nov 15;371(2):317-25
10545220
Biochem Biophys Res Commun. 1990 Feb 28;167(1):148-53
2310386
Toxicol Appl Pharmacol. 1997 Dec;147(2):431-41
9439738
J Cell Biol. 1969 Jul;42(1):1-45
4891913
Proc Natl Acad Sci U S A. 2002 Feb 19;99(4):2380-5
11854531
Circulation. 1975 Jan;51(1):39-67
122789
Biophys J. 2006 Dec 1;91(11):4317-27
16980364
J Cell Biol. 2000 Sep 18;150(6):1283-98
10995435
J Bioenerg Biomembr. 2005 Jun;37(3):129-42
16167170
J Cell Biol. 1992 Apr;117(2):337-45
1373142
Cardiovasc Res. 2008 Jan 15;77(2):432-41
18006452
Am J Pathol. 1964 Mar;44:491-505
14126668
Biochem J. 1999 Oct 15;343 Pt 2:311-7
10510294
J Physiol. 2000 Nov 15;529 Pt 1:37-47
11080249
Adv Exp Med Biol. 1992;311:245-62
1529757
Annu Rev Pharmacol Toxicol. 2001;41:317-45
11264460
Science. 1993 Oct 29;262(5134):740-4
8235594
Biophys J. 1998 Mar;74(3):1149-68
9512016
Cardiovasc Res. 1993 Oct;27(10):1800-9
8275527
Adv Exp Med Biol. 1997;419:411-9
9193683
Biochem Pharmacol. 1970 Jan;19(1):197-207
4323654
Biophys J. 2000 Sep;79(3):1273-84
10968991
Cardiovasc Pathol. 2000 Jan-Feb;9(1):1-8
10739901
Mol Cell Biochem. 2004 Jan-Feb;256-257(1-2):331-9
14977192
Biophys J. 2007 Feb 1;92(3):1058-71
17098804
Biull Eksp Biol Med. 1982 Jul;94(7):116-8
7126812
J Biol Chem. 1977 Dec 10;252(23):8731-9
925018
Arch Biochem Biophys. 1979 Jul;195(2):460-7
38751
J Bioenerg Biomembr. 1998 Jun;30(3):207-22
9733088
Mol Cell Biochem. 2004 Jan-Feb;256-257(1-2):185-99
14977180
J Biol Chem. 2001 Jan 26;276(4):2586-99
11029457
Nature. 2003 Dec 18;426(6968):862-6
14685243
Biophys J. 2008 Sep 15;95(6):3079-99
18757564
Science. 1990 Oct 26;250(4980):565-8
2173135
Cardiovasc Res. 2003 Mar 15;57(4):897-912
12650868
J Physiol. 1992;453:591-608
1464847
Biophys J. 2006 Aug 15;91(4):1564-89
16679365
Biochim Biophys Acta. 2006 May-Jun;1757(5-6):509-17
16829228
Biophys J. 1998 Oct;75(4):2004-14
9746542
Mol Cell Biochem. 2004 Jan-Feb;256-257(1-2):107-15
14977174
J Mol Cell Cardiol. 2002 Aug;34(8):941-50
12234764
J Cell Biol. 1982 Jun;93(3):883-92
6749864
J Neurophysiol. 2002 Feb;87(2):740-9
11826043
Circ Res. 1998 Nov 2;83(9):898-907
9797338
Free Radic Res. 2004 Oct;38(10):1113-8
15512800
Am J Physiol. 1990 May;258(5 Pt 1):C755-86
2185657
Nature. 1995 Oct 5;377(6548):438-41
7566122
J Gen Physiol. 1999 Mar;113(3):469-89
10051521
Cardiovasc Res. 2007 Mar 1;73(4):631-40
17157285
J Neurochem. 2002 Feb;80(4):706-14
11841577
J Biol Chem. 2001 Aug 24;276(34):32257-63
11413128
Biophys J. 2002 Aug;83(2):587-604
12124250
J Mol Cell Cardiol. 1998 Oct;30(10):2013-23
9799655
J Bioenerg Biomembr. 1987 Aug;19(4):309-20
3305491
Front Biosci. 2002 Jul 1;7:d1697-711
12086924
J Biol Chem. 2000 May 19;275(20):15305-13
10809765
Biophys J. 1989 Aug;56(2):229-42
2673420
J Physiol. 1995 Sep 15;487 ( Pt 3):601-8
8544124
J Muscle Res Cell Motil. 2006;27(5-7):297-306
16897575
Am J Physiol. 1998 Jan;274(1):H8-17
9458846
J Biol Chem. 2001 Aug 3;276(31):29430-9
11358971
J Physiol. 1999 Jul 1;518(Pt 1):173-86
10373699
Biochim Biophys Acta. 2007 Jul;1768(7):1784-95
17499575
FEBS Lett. 1980 Mar 10;111(2):261-8
6987089
Circ Res. 2000 Aug 4;87(3):201-6
10926870
J Cell Biol. 1969 Jul;42(1):46-67
5786989
Am J Physiol Cell Physiol. 2006 Nov;291(5):C840-50
16723510
Proc R Soc Lond B Biol Sci. 1984 Dec 22;223(1231):239-54
6151662
Am J Physiol. 1994 Aug;267(2 Pt 1):C313-39
8074170
J Biol Chem. 2000 Jul 14;275(28):21566-71
10781610
J Biol Chem. 1991 Feb 25;266(6):3376-9
1847371
J Physiol. 2001 Oct 15;536(Pt 2):387-96
11600674
Physiol Rev. 1994 Jul;74(3):595-636
8036248
Pharmacol Toxicol. 1998 Nov;83(5):214-9
9834970
Physiology (Bethesda). 2008 Apr;23:84-94
18400691
Curr Opin Struct Biol. 2000 Oct;10(5):548-56
11042452
J Bioenerg Biomembr. 1994 Oct;26(5):509-17
7896766
EMBO J. 2002 May 1;21(9):2198-206
11980717
Eur J Pharmacol. 1997 Dec 11;340(2-3):295-300
9537826
Cell. 2002 Nov 1;111(3):331-42
12419244
Circ Res. 2002 Aug 23;91(4):315-22
12193464
Biophys J. 2002 Jul;83(1):59-78
12080100
Physiol Rev. 2008 Oct;88(4):1491-545
18923188
Biophys J. 2004 Jul;87(1):696-713
15240503
Cell Calcium. 2008 Jul;44(1):77-91
18178248
Am J Physiol. 1997 Aug;273(2 Pt 1):C717-33
9277370
J Biol Chem. 1998 Apr 24;273(17):10223-31
9553073
Biochim Biophys Acta. 1995 Jul 17;1241(2):139-76
7640294
Pflugers Arch. 1996 Oct;432(6):1047-54
8781199
Am J Physiol Heart Circ Physiol. 2007 Jul;293(1):H307-13
17351070
Curr Med Chem. 2003 Jun;10(11):967-81
12678683
Cell. 2003 Nov 26;115(5):629-40
14651853
J Cell Biol. 1987 May;104(5):1343-52
3553210
Mol Cell Biochem. 2004 Jan-Feb;256-257(1-2):341-58
14977193
Recent Adv Stud Cardiac Struct Metab. 1976 May 26-29;12:471-5
145642
J Bioenerg Biomembr. 2000 Feb;32(1):97-104
11768767
Annu Rev Biomed Eng. 2001;3:57-81
11447057
Ann Biomed Eng. 2002 Jun;30(6):808-27
12220081
Biophys J. 2001 Jan;80(1):103-20
11159386
Am J Physiol Cell Physiol. 2007 Jun;292(6):C2004-20
17344315
Biophys J. 2000 Jan;78(1):322-33
10620296
Biophys J. 2006 Feb 1;90(3):1107-19
16284268
Proc Natl Acad Sci U S A. 2005 Feb 22;102(8):3099-104
15710901
J Cell Biol. 2004 Feb 16;164(4):493-9
14769861
Biochem Biophys Res Commun. 1997 May 8;234(1):252-6
9168998
Biochem Biophys Res Commun. 1995 Apr 6;209(1):167-74
7726831
Science. 1993 Oct 29;262(5134):744-7
8235595
J Membr Biol. 2002 May 15;187(2):147-56
12029371
J Bioenerg Biomembr. 2004 Aug;36(4):277-81
15377857
Drug Discov Today Dis Models. 2007;4(4):207-217
18650959
Biophys J. 2005 Sep;89(3):1893-901
15980179
Chem Immunol. 2000;75:121-45
10851782
J Mol Cell Cardiol. 2000 Nov;32(11):1981-94
11040103
J Biol Chem. 2008 Nov 21;283(47):32771-80
18790739
Biochim Biophys Acta. 1996 Jun 13;1274(3):81-8
8664307
Circ Res. 2001 Sep 14;89(6):526-33
11557740
Nat Biotechnol. 2003 Mar;21(3):281-6
12592411
Cell Calcium. 2008 Jul;44(1):51-63
18242694
Ann N Y Acad Sci. 1998 Sep 16;853:341-4
10603975
J Physiol. 2008 Jul 1;586(13):3267-85
18467367
Ann N Y Acad Sci. 1998 Sep 16;853:20-30
10603933
Circulation. 2001 Mar 20;103(11):1577-84
11257088
Biophys J. 1999 Sep;77(3):1528-39
10465763
Prog Biophys Mol Biol. 2004 Jun-Jul;85(2-3):141-62
15142741
Circ Res. 2001 Jul 20;89(2):153-9
11463722
Proc Natl Acad Sci U S A. 2006 May 16;103(20):7906-10
16672364
J Biol Chem. 2000 Nov 10;275(45):35402-7
10958797
Biochim Biophys Acta. 2001 Apr 2;1504(2-3):248-61
11245789
Biochem J. 2000 Nov 15;352 Pt 1:61-70
11062058
J Bioenerg Biomembr. 2000 Feb;32(1):15-25
11768758
Am J Physiol. 1992 Aug;263(2 Pt 1):C545-50
1514597
J Membr Biol. 1995 Jul;146(2):133-44
7473684
Anticancer Drugs. 2002 Nov;13(10):1017-29
12439336
Am J Physiol. 1998 Apr;274(4):C1174-84
9575814
Biochem Biophys Res Commun. 2000 Dec 29;279(3):858-63
11162440
Biochem J. 2001 Feb 1;353(Pt 3):531-6
11171049
Cardiovasc Res. 1999 Dec;44(3):556-67
10690288
J Mol Cell Cardiol. 2001 Apr;33(4):615-24
11273716
Am J Physiol Heart Circ Physiol. 2005 Apr;288(4):H1820-8
15563537
Biochem J. 2001 Jun 1;356(Pt 2):643-57
11368796
Cell Calcium. 2003 Apr;33(4):247-56
12618145
Basic Res Cardiol. 2007 Sep;102(5):369-92
17657400
Circ Res. 2002 Oct 4;91(7):594-600
12364387
Biochem J. 1997 Sep 1;326 ( Pt 2):401-5
9291111
Circ Res. 2005 Jan 7;96(1):82-90
15569829
J Neurochem. 2002 Feb;80(3):405-15
11905989
J Physiol. 2000 Feb 15;523 Pt 1:29-44
10673543
Circ Res. 2000 Dec 8;87(12):1087-94
11110764
Biophys J. 2002 Jan;82(1 Pt 1):193-205
11751308
Biochem J. 2001 Aug 15;358(Pt 1):147-55
11485562
Nature. 2006 Oct 12;443(7112):658-62
17035996
Trends Pharmacol Sci. 1993 Nov;14(11):408-13
8296399
Biophys J. 1998 Dec;75(6):2801-10
9826602
J Mol Cell Cardiol. 1997 Sep;29(9):2441-50
9299367
Biochim Biophys Acta. 2002 Dec 2;1556(2-3):155-67
12460673
Circ Res. 1976 Mar;38(3):156-62
1248063
J Biol Chem. 1995 Nov 17;270(46):27510-5
7499209
Circ Res. 1987 Mar;60(3):327-36
2953507
Circ Res. 1991 May;68(5):1378-89
2018996
Pflugers Arch. 2001 Feb;441(5):674-7
11294249
Philos Trans A Math Phys Eng Sci. 2008 Sep 28;366(1879):3381-409
18603526
Am J Physiol. 1991 Oct;261(4 Pt 2):H1123-34
1928394
Anat Rec. 1980 May;197(1):33-48
7425305
J Clin Invest. 2005 Dec;115(12):3527-35
16284648
J Biol Chem. 2001 Jun 15;276(24):21482-8
11297554
J Biol Chem. 1996 Mar 29;271(13):7398-403
8631764
J Biol Chem. 1982 Feb 10;257(3):1540-8
6460026
Circ Res. 2002 Aug 23;91(4):276-7
12193458
Circ Res. 1996 Jan;78(1):166-71
8603501
J Physiol. 1999 Jul 15;518 ( Pt 2):433-47
10381590
Mol Cell Biochem. 2002 Sep;238(1-2):119-27
12349899
Science. 1990 Apr 20;248(4953):283
2326638
Ann N Y Acad Sci. 2005 Jun;1047:127-37
16093491
Proc Natl Acad Sci U S A. 1998 Feb 17;95(4):1484-9
9465041
Nature. 2002 Jan 10;415(6868):198-205
11805843
Cell Calcium. 2002 Feb;31(2):97-104
11969250
J Biol Chem. 2001 Jun 29;276(26):24145-52
11328820
J Bioenerg Biomembr. 2008 Jun;40(3):163-70
18654841
J Biol Chem. 2002 Sep 13;277(37):33664-9
12087096
J Physiol. 1994 Feb 1;474(3):463-71
8014907
Int J Biochem. 1993 Apr;25(4):589-96
8385638
J Physiol. 1997 Jan 1;498 ( Pt 1):31-47
9023766
J Cell Biol. 1999 Nov 15;147(4):809-22
10562282
Cell. 2008 Jul 25;134(2):279-90
18662543
Biochem J. 1996 Oct 1;319 ( Pt 1):143-8
8870661
Circ Res. 2006 Jul 21;99(2):172-82
16778127
Curr Opin Chem Biol. 2000 Dec;4(6):653-60
11102870
Circ Res. 2003 Apr 4;92(6):651-8
12600875
J Mol Med (Berl). 2000;78(1):26-35
10759027
Circ Res. 2001 Sep 28;89(7):614-22
11577027
J Physiol. 2005 Jun 15;565(Pt 3):855-72
15845582
Cell Physiol Biochem. 2002;12(5-6):269-78
12438763
Am J Physiol. 1998 Apr;274(4):C1158-73
9575813
J Physiol. 1999 Jul 15;518 ( Pt 2):577-84
10381602
Mol Cell Biochem. 2000 Jul;210(1-2):153-8
10976768
Trends Biochem Sci. 2000 Jul;25(7):319-24
10871882