title: Mitochondrial stress signaling in longevity: a new role for mitochondrial function in aging.
abstract: Mitochondria are principal regulators of cellular function and metabolism through production of ATP for energy homeostasis, maintenance of calcium homeostasis, regulation of apoptosis and fatty acid oxidation to provide acetyl CoA for fueling the electron transport chain. In addition, mitochondria play a key role in cell signaling through production of reactive oxygen species that modulate redox signaling. Recent findings support an additional mechanism for control of cellular and tissue function by mitochondria through complex mitochondrial-nuclear communication mechanisms and potentially through extracellular release of mitochondrial components that can act as signaling molecules. The activation of stress responses including mitophagy, mitochondrial number, fission and fusion events, and the mitochondrial unfolded protein response (UPR(MT)) requires mitochondrial-nuclear communication for the transcriptional activation of nuclear genes involved in mitochondrial quality control and metabolism. The induction of these signaling pathways is a shared feature in long-lived organisms spanning from yeast to mice. As a result, the role of mitochondrial stress signaling in longevity has been expansively studied. Current and exciting studies provide evidence that mitochondria can also signal among tissues to up-regulate cytoprotective activities to promote healthy aging. Alternatively, mitochondria release signals to modulate innate immunity and systemic inflammatory responses and could consequently promote inflammation during aging. In this review, established and emerging models of mitochondrial stress response pathways and their potential role in modulating longevity are discussed.
authors.affiliation: Free Radical Biology and Aging Research Program, Oklahoma Medical Research Foundation, 825 N.E. 13th Street, Oklahoma City, OK 73104, USA ; Oklahoma City VA Medical Center, Oklahoma City, OK, USA ; Department of Cellular and Structural Biology, University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Drive, San Antonio, TX 78229, USA ; Barshop Institute for Longevity and Aging Studies, University of Texas Health Science Center at San Antonio, San Antonio, TX, USA.
authors.forename: Shauna
authors.initials: S
authors.lastname: Hill
authors.affiliation: Free Radical Biology and Aging Research Program, Oklahoma Medical Research Foundation, 825 N.E. 13th Street, Oklahoma City, OK 73104, USA ; Oklahoma City VA Medical Center, Oklahoma City, OK, USA.
authors.forename: Holly
authors.initials: H
authors.lastname: Van Remmen
mesh_terms: D000375:Aging / Q000378:metabolism*; D000818:Animals; D006801:Humans; D008136:Longevity; D008928:Mitochondria / Q000378:metabolism*; D018384:Oxidative Stress; D015398:Signal Transduction
keywords: Longevity; Mitochondria; Mitochondrial signaling; Mitochondrial unfolded protein response; Retrograde response