NADNADH and NADPNADPH in Cellular Functions and

NADNADH and NADPNADPH in Cellular Functions and

ABSTRACT
Accumulating evidence has suggested that NAD (including NAD and NADH) and NADP (including NADP
and NADPH) could belong to the fundamental common mediators of various biological processes, including
energy metabolism, mitochondrial functions, calcium homeostasis, antioxidation/generation of oxidative stress,
gene expression, immunological functions, aging, and cell death: First, it is established that NAD mediates energy
metabolism and mitochondrial functions; second, NADPH is a key component in cellular antioxidation
systems; and NADH-dependent reactive oxygen species (ROS) generation from mitochondria and NADPH
oxidase-dependent ROS generation are two critical mechanisms of ROS generation; third, cyclic ADP-ribose
and several other molecules that are generated from NAD and NADP could mediate calcium homeostasis;
fourth, NAD and NADP modulate multiple key factors in cell death, such as mitochondrial permeability transition,
energy state, poly(ADP-ribose) polymerase-1, and apoptosis-inducing factor; and fifth, NAD and NADP
profoundly affect aging-influencing factors such as oxidative stress and mitochondrial activities, and NADdependent
sirtuins also mediate the aging process. Moreover, many recent studies have suggested novel paradigms
of NAD and NADP metabolism. Future investigation into the metabolism and biological functions of
NAD and NADP may expose fundamental properties of life, and suggest new strategies for treating diseases
and slowing the aging process. Antioxid. Redox Signal. 10, 179–206…

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