Presentation is loading. Please wait.

Presentation is loading. Please wait.

1  Increases ATP production  Ca 2+ homeostasis  Fatigue/disease/apoptosis/cell death  Protein synthesis  Signals to new sites e.g. RYR, IP 3 Mitochondria.

Similar presentations


Presentation on theme: "1  Increases ATP production  Ca 2+ homeostasis  Fatigue/disease/apoptosis/cell death  Protein synthesis  Signals to new sites e.g. RYR, IP 3 Mitochondria."— Presentation transcript:

1 1  Increases ATP production  Ca 2+ homeostasis  Fatigue/disease/apoptosis/cell death  Protein synthesis  Signals to new sites e.g. RYR, IP 3 Mitochondria and Ca 2+ Why bother?

2 2 Rizzuto et al., Oncogene (2003) 22,

3 3 Maternally transmitted Polarised -150 – 200 mV More cristae = more ATP Epithelial cells, few Muscle, up to 1000 per cell

4 4 How to tackle mitochondria?  Since 1961, isolate them from tissue alter function, lose regulatory factors  Since early 1990’s, study them in situ –O 2 consumption, intrinsic fluorescence, –Use fluorescent dyes (Ca 2+, ROS, Memb. pot.)

5 5 CGP Mitochondrial Ca 2+ entry and release

6 6 Blocking Ca 2+ entry and exit  Depolarise mitochondria: FCCP  Inhibit Ca 2+ uniporter: Ru360  Na + -Ca 2+ exchanger: CGP37157  H + -Ca 2+ exchanger ?  MTP: Cyclosporin A ??

7 7, Na +, K + Mitochondria selectively take up Ca 2+ but no other physiologically relevant ion. Kirichok et al., Nature (2004) 427,

8 8 Mitochondrial mysteries Structures of all Ca 2+ transport related proteins are unknown. Structure of mitochondrial transition pore (MTP, PTP, MPTP) also unknown. Mitochondrial myopathies.

9 9 Mouse muscle 10–15% fibre volume Denser at surface Fixed positions with desmin + plectin Close to Ca 2+ release site

10 10 In mammalian muscle, mitochondria are near transverse tubules

11 11 Csordás et al., Trends Cardiovasc Med

12 12 General model of Ca 2+ stimulation of ROS production

13 13 Measure mitochondrial Ca 2+ and ROS simultaneously

14 14 In motor neurones, mitochondria limit increase in cytosolic Ca 2+ Cytosol Mitochondria David et al. J Physiol , 59-65

15 15 Useful links for confocal users home/support/Tutorials.htmlhttp://www.invitrogen.com/site/us/en/ home/support/Tutorials.html


Download ppt "1  Increases ATP production  Ca 2+ homeostasis  Fatigue/disease/apoptosis/cell death  Protein synthesis  Signals to new sites e.g. RYR, IP 3 Mitochondria."

Similar presentations


Ads by Google