SR/ER -mitochondria coupling Excitation-metabolism coupling Lin GH 2004.4
Excitation-metabolism coupling SR/ER – mitochondria coupling 2004.4 Lin GH &
Structural coupling between SR/ER and mitochondria ER-mitochondrialjunction
Structural coupling between SR/ER and mitochondria ER—mitochondrial junction
Functional coupling between ER/SR and mitochondria 【ca21 n signals coupled to【Ca21 eoscillations [Ca2*Im Cell 1 Cell 2 (Fmod2)i iv v vi ii il iv v vi Fnuo3) 160- NECA NECA 50 140 120 100 80 33 90 120 Time (s)9 90 120 Simultaneous confocal imaging of IPR 10m driven [Ca2+]c and [Ca2+]m signals RBL-2H3 cells
Functional coupling between ER/SR and mitochondria Simultaneous confocal imaging of IP3R driven [Ca2+]c and [Ca2+]m signals [Ca2+]m signals coupled to [Ca2+]c oscillations RBL-2H3 cells
900 +5 mM Caffeine Time(s) Time(s) 172 180s 26 Coordination of RyR driven [Ca2+]c and [Ca2+]m oscillations
Coordination of RyR driven [Ca2+]c and [Ca2+]m oscillations
A Ca2*]m +Caffeine:0.5 mM 5mM [Ca21 1539 1689 405s 420s Ca2*1 [Ca2] [Ca2*]m200 5 mM Caffeine [Ca2*]c (f.a.u.) 150 0.5 mM Caffeine 6o(f.a.u.) 5 um 100 ww Confocal imaging of 060 120180240300360420480540 600 localized and global Time(s) [Ca2+]m and [Ca2+]c responses H9c2 cardiac myotubes
Confocal imaging of localized and global [Ca2+ ] m and [Ca 2 + ] c responses H9c2 cardiac myotubes
(B) Marks Width (um)Duration(ms) permeabilized: 0.59±0.02173.9±8.4 [Ca2+]m 2 um 100ms Ca2+marks miniature calcium signals in single mitochondria driven by ryanodine receptors Sparks intact 2.86±0.04 51.5±1.5 15 um 100 1.90±0.03 37.4±1.4 [Ca2+]sparks and [Ca2+]m marks
[Ca2+ ]c sparks and [Ca2+ ]m marks Ca2+ marks miniature calcium signals in single mitochondria driven by ryanodine receptors
Local [Ca2+]control between SR and mitochondria Mitochondrial Ca2+Uptake SR The Ca2+uptake can be divided into the following three steps: (1)Ca2+movement from the SR-mite efch DA IP3R/RyR to OMM OMM (2)Ca2+transpot through OMM (3)Ca2+transportthrough IMM. Mitochondrial Cabuffers OMM:outer mitochondrial membrane IMM:inner mitochondrial membrane Mitochondrial matrix
The Ca2+ uptake can be divided into the following three steps: (1) Ca2+ movement from the IP3R/RyR to OMM (2) Ca2+ transpot through OMM (3) Ca2+ transport through IMM. OMM:outer mitochondrial membrane IMM: inner mitochondrial membrane Mitochondrial Ca2+ Uptake
Mitochondrial Ca2+Uptake H a2 VDAC Calcium permeation through the OMM Through the OMM,the voltage-dependent anion channels (VDAC,porin)have been thought to permit free passage of ions and other small molecules.However,recent studies suggest that the VDAC may represent a regulated step in Ca2+transport from IP R/RyR to the IMM
Through the OMM, the voltage-dependent anion channels (VDAC, porin) have been thought to permit free passage of ions and other small molecules. However, recent studies suggest that the VDAC may represent a regulated step in Ca2+ transport from IP3R/RyR to the IMM. Mitochondrial Ca2+ Uptake
Mitochondrial Ca2+Uptake VDAC Calcium permeation through the IMM rapid uptake mode(RaM) mitochondrial Ca2+uniporter
rapid uptake mode (RaM) mitochondrial Ca2+ uniporter Mitochondrial Ca2+ Uptake
Mitochondrial Ca2+Efflux Ca aM 32 opening of the permeability transition VDAC pore(PTP) ion-exchangers 3Na+/Ca2+exchanger(predominates in heart muscle) ·3H+/Ca2+exchanger
Mitochondrial Ca2+ Efflux ion-exchangers • 3Na+/Ca2+ exchanger (predominates in heart muscle) • 3H+/Ca2+ exchanger ? opening of the permeability transition pore (PTP)