Chapter 325 - Signaling Pathways from Mitochondria to the Nucleus

Abstract

Mitochondrial research has entered a new era, which recognizes that mitochondria are key players in intracellular signaling. Cells monitor and respond to changes in the functional state of their mitochondria, resulting in responses as severe as apoptosis and as subtle as changes in nuclear gene expression. The general term for this mitochondriato- nucleus signaling is retrograde regulation. In animal cells, compromises in mitochondrial function often lead to increases in mitochondrial biogenesis, with attendant increases in mitochondrial DNA levels and mitochondrial gene expression. In many instances, changes also occur in the expression of nonmitochondrial components associated with mitochondrial dysfunctions. Many of these effects are signaled by intra- and extracellular glutamate levels. In both yeast and filamentous fungi, the retrograde response is intimately tied to aging and cellular senescence. Altogether, retrograde regulation adapts cells to increased energy demands, and links mitochondrial function to fundamental processes of nutrient sensing, carbohydrate and nitrogen metabolism, stress, and aging.