Shaping mitochondrial dynamics: The role of cAMP signalling

Biochem Biophys Res Commun. 2018 May 27;500(1):65-74. doi: 10.1016/j.bbrc.2017.05.041. Epub 2017 May 10.

Abstract

In recent years, our idea of mitochondria evolved from "mere" energy and metabolite producers to key regulators of many cellular functions. In order to preserve and protect their functional status, these organelles engage a number of dynamic processes that allow them to decrease accumulated burden and maintain their homeostasis. Indeed, mitochondria can unite (fusion), divide (fission), position themselves strategically in the cell (motility/trafficking) and if irreversibly damaged or dysfunctional eliminated (mitophagy). These dynamic processes can be controlled both by mitochondrial and cellular signalling pathways, hence allowing mitochondria to tune their function to the cellular needs. Among the regulatory mechanisms, reversible phosphorylation downstream the cyclic AMP (cAMP) signalling cascade was shown to deeply influence mitochondrial dynamics. This review explores the emerging evidence suggesting that cAMP is a key player in the orchestration of mitochondrial fusion/fission, motility and mitophagy, extending the repertoire of this second messenger, which is now recognised as a major regulator of mitochondrial homeostasis.

Keywords: Mitochondria; Mitochondrial dynamics; Mitophagy; PKA; cAMP.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Calcium / metabolism
  • Cyclic AMP / metabolism*
  • Cyclic AMP-Dependent Protein Kinases / genetics
  • Cyclic AMP-Dependent Protein Kinases / metabolism
  • Dynamins
  • GTP Phosphohydrolases / genetics
  • GTP Phosphohydrolases / metabolism
  • Gene Expression Regulation
  • Homeostasis / genetics
  • Humans
  • Microtubule-Associated Proteins / genetics
  • Microtubule-Associated Proteins / metabolism
  • Mitochondria / metabolism*
  • Mitochondrial Dynamics / genetics*
  • Mitochondrial Membrane Transport Proteins / genetics
  • Mitochondrial Membrane Transport Proteins / metabolism
  • Mitochondrial Proteins / genetics
  • Mitochondrial Proteins / metabolism
  • Mitophagy / genetics*
  • Movement
  • Phosphorylation
  • Signal Transduction / genetics*

Substances

  • Microtubule-Associated Proteins
  • Mitochondrial Membrane Transport Proteins
  • Mitochondrial Proteins
  • Cyclic AMP
  • Cyclic AMP-Dependent Protein Kinases
  • GTP Phosphohydrolases
  • MFN2 protein, human
  • Mfn1 protein, human
  • DNM1L protein, human
  • Dynamins
  • Calcium