TY - JOUR
T1 - Elevated mitochondria-coupled NAD(P)H in endoplasmic reticulum of dopamine neurons
AU - Tucker, Kristal R.
AU - Cavolo, Samantha L.
AU - Levitan, Edwin S.
N1 - Publisher Copyright:
© 2016 Snowdon and Johnston.
PY - 2016/11/1
Y1 - 2016/11/1
N2 - Pyridine nucleotides are redox coenzymes that are critical in bioenergetics, metabolism, and neurodegeneration. Here we use brain slice multiphoton microscopy to show that substantia nigra dopamine neurons, which are sensitive to stress in mitochondria and the endoplasmic reticulum (ER), display elevated combined NADH and NADPH (i.e., NAD(P)H) auto?uorescence. Despite limited mitochondrial mass, organellar NAD(P)H is extensive because much of the signal is derived from the ER. Remarkably, even though pyridine nucleotides cannot cross mitochondrial and ER membranes, inhibiting mitochondrial function with an uncoupler or interrupting the electron transport chain with cyanide (CN-) alters ER NAD(P)H. The ER CN-response can occur without a change in nuclear NAD(P)H, raising the possibility of redox shuttling via the cytoplasm locally between neuronal mitochondria and the ER. We propose that coregulation of NAD(P)H in dopamine neuron mitochondria and ER coordinates cell redox stress signaling by the two organelles.
AB - Pyridine nucleotides are redox coenzymes that are critical in bioenergetics, metabolism, and neurodegeneration. Here we use brain slice multiphoton microscopy to show that substantia nigra dopamine neurons, which are sensitive to stress in mitochondria and the endoplasmic reticulum (ER), display elevated combined NADH and NADPH (i.e., NAD(P)H) auto?uorescence. Despite limited mitochondrial mass, organellar NAD(P)H is extensive because much of the signal is derived from the ER. Remarkably, even though pyridine nucleotides cannot cross mitochondrial and ER membranes, inhibiting mitochondrial function with an uncoupler or interrupting the electron transport chain with cyanide (CN-) alters ER NAD(P)H. The ER CN-response can occur without a change in nuclear NAD(P)H, raising the possibility of redox shuttling via the cytoplasm locally between neuronal mitochondria and the ER. We propose that coregulation of NAD(P)H in dopamine neuron mitochondria and ER coordinates cell redox stress signaling by the two organelles.
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U2 - 10.1091/mbc.E16-07-0479
DO - 10.1091/mbc.E16-07-0479
M3 - Article
C2 - 27582392
AN - SCOPUS:84994355501
SN - 1059-1524
VL - 27
SP - 3214
EP - 3220
JO - Molecular biology of the cell
JF - Molecular biology of the cell
IS - 21
ER -