Mitochondrial stress signaling in longevity: A new role for mitochondrial function in aging

Shauna Hill, Holly Van Remmen

Research output: Contribution to journalReview articlepeer-review

67 Scopus citations

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 (UPRMT) 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.

Original languageEnglish (US)
Pages (from-to)936-944
Number of pages9
JournalRedox Biology
Volume2
Issue number1
DOIs
StatePublished - 2014

Keywords

  • Longevity
  • Mitochondria
  • Mitochondrial signaling
  • Mitochondrial unfolded protein response
  • Retrograde response

ASJC Scopus subject areas

  • Organic Chemistry
  • Clinical Biochemistry

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