IBIMOL   23987
INSTITUTO DE BIOQUIMICA Y MEDICINA MOLECULAR PROFESOR ALBERTO BOVERIS
Unidad Ejecutora - UE
capítulos de libros
Título:
Nitric Oxide. Biology and Pathobiology. 2nd ed.
Autor/es:
BOVERIS A; CARRERAS MC; PODEROSO JJ
Libro:
The regulation of cell energetics and mitochondrial signaling by nitric oxide
Editorial:
Academic Press
Referencias:
Año: 2010; p. 441 - 482
Resumen:
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The
recognition that NO is a reversible inhibitor of cytochrome oxidase activity
competitively
with O2 produced a copernican revolution in the understanding of the
regulation
of respiration, specially at low tissue pO2. It is now understood that tissue
O2
uptake
depends on the O2/NO ratio, a concept that has both experimental and
mathematical
support. Mitochondrial O2- production, stimulated by NO itself, removes
the
NO-inhibition of cytochrome oxidase providing the reversibility of the
regulatory
mechanism.
The calculated intramitochondrial NO levels (100-360 nM) are in the range
of the
concentrations, 80-200 nM NO, that inhibit by 50 % cytochrome oxidase activity.
Mitochondria
have their own source of NO with mtNOS, a transcript of nNOS-a, an
integral
protein of the inner membrane and a voltage-dependent enzyme, whose activity
inhibits
mitochondrial O2 uptake. Mitochondrial NO has a role in cell signaling:
decreased
mtNOS activity leads to cell proliferation and increased mtNOS activity leads
to cell
arrest. Over stimulated mtNOS activity and increased NO mitochondrial levels
are
associated with mitochondrial dysfunction and nitrative and nitrosative stress
in a
series of pathophysiological conditions.