The Role of Mitochondria in Signaling

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The Role of Mitochondria in Signaling

• Shey-Shing Sheu, Ph.D.
• Department of Pharmacology and Physiology
• School of Medicine and Dentistry
• University of Rochester

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The General Organization of a Mitochondrion
Fawcett, A Textbook of Histology, Chapman and
Hall, 12th edition, 1994
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Mitochondrial ?? Transients and Movement in
Cultured Striatal Neurons
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• Mitochondria are the powerhouse of the cell.
• Mitochondria have the largest buffering capacity
  for cell Ca2.
• Mitochondria are the major sources of reactive
  oxygen species (ROS).
• Mitochondrial defects play a key role in aging,
  degenerative diseases, and cancer.

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Mitochondrial Bioenergetics
CYTOPLASM
VDAC
Cyanide Azide H2S CO
Rotenone Piericidin MPP
Antimycin
Q
Cyt C
e-
Complex III
Complex I NADH Dehydrogenase
NADH H
Complex IV Cytochrome Oxidase
O2
NAD
e-
e-
Dehydrogenases
3-NPA Malonate
H2O
Complex II Succinate Dehydrogenase
ADP Pi
H
Glycerol Phosphate Dehydrogenase (Flavoprotein)
Fumarate
Succinate
H
TCA
Malate
Succinyl CoA
H
Complex V ATP Synthase
Dihydroxyacetone Phosphate
Glycerol Phosphate
ATP
Oxaloacetate
a-Ketoglutarate
Citrate
Acetyl CoA
Aspartate
MITOCHONDRION
Pyruvate
Lactate
Aspartate
Malate
Glycerol Phosphate
Dihydroxyacetone Phosphate
NAD
LDH
Oxaloacetate
NADH
NADH
NAD
NADH
NAD
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Mitochondrial Calcium Homeostasis
CGP37157
VDAC
nMV-CsA
2Na
2H
H
Cyt-c
Ca2
ATP
ADP
MPTP
ANT
ATP
Ca2
Uni
Ca2