Mitochondrial signal transduction

Martin Picard, Orian S. Shirihai

Research output: Contribution to journalReview articlepeer-review

109 Scopus citations


The analogy of mitochondria as powerhouses has expired. Mitochondria are living, dynamic, maternally inherited, energy-transforming, biosynthetic, and signaling organelles that actively transduce biological information. We argue that mitochondria are the processor of the cell, and together with the nucleus and other organelles they constitute the mitochondrial information processing system (MIPS). In a three-step process, mitochondria (1) sense and respond to both endogenous and environmental inputs through morphological and functional remodeling; (2) integrate information through dynamic, network-based physical interactions and diffusion mechanisms; and (3) produce output signals that tune the functions of other organelles and systemically regulate physiology. This input-to-output transformation allows mitochondria to transduce metabolic, biochemical, neuroendocrine, and other local or systemic signals that enhance organismal adaptation. An explicit focus on mitochondrial signal transduction emphasizes the role of communication in mitochondrial biology. This framework also opens new avenues to understand how mitochondria mediate inter-organ processes underlying human health.

Original languageEnglish
Pages (from-to)1620-1653
Number of pages34
JournalCell Metabolism
Issue number11
StatePublished - 1 Nov 2022
Externally publishedYes


  • amplification
  • communication
  • energy
  • evolution
  • health
  • membrane potential
  • metabokines
  • mito-nuclear signaling
  • mitochondrial networks
  • mitokines
  • mitotypes
  • receptors
  • signal transduction
  • steroid hormones
  • stress responses
  • tissue-specific

ASJC Scopus subject areas

  • Molecular Biology
  • Physiology
  • Cell Biology


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