IP(3) Receptors, Mitochondria, and Ca Signaling: Implications for Aging.

The tight interplay between endoplasmic-reticulum-(ER-) and mitochondria-mediated Ca(2+) signaling is a key determinant of cellular health and cellular fate through the control of apoptosis and autophagy. Proteins that prevent or promote apoptosis and autophagy can affect intracellular Ca(2+) dynamics and homeostasis through binding and modulation of the intracellular Ca(2+)-release and Ca(2+)-uptake mechanisms. During aging, oxidative stress becomes an additional factor that affects ER and mitochondrial function and thus their role in Ca(2+) signaling. Importantly, mitochondrial dysfunction and sustained mitochondrial damage are likely to underlie part of the aging process. In this paper, we will discuss the different mechanisms that control intracellular Ca(2+) signaling with respect to apoptosis and autophagy and review how these processes are affected during aging through accumulation of reactive oxygen species.