Mitochondrial Ca(2+) Mobilization Is a Key Element in Olfactory Signaling

Nat Neurosci. 2012 Mar 25;15(5):754-62. doi: 10.1038/nn.3074.

Abstract

In olfactory sensory neurons (OSNs), cytosolic Ca(2+) controls the gain and sensitivity of olfactory signaling. Important components of the molecular machinery that orchestrates OSN Ca(2+) dynamics have been described, but key details are still missing. Here, we demonstrate a critical physiological role of mitochondrial Ca(2+) mobilization in mouse OSNs. Combining a new mitochondrial Ca(2+) imaging approach with patch-clamp recordings, organelle mobility assays and ultrastructural analyses, our study identifies mitochondria as key determinants of olfactory signaling. We show that mitochondrial Ca(2+) mobilization during sensory stimulation shapes the cytosolic Ca(2+) response profile in OSNs, ensures a broad dynamic response range and maintains sensitivity of the spike generation machinery. When mitochondrial function is impaired, olfactory neurons function as simple stimulus detectors rather than as intensity encoders. Moreover, we describe activity-dependent recruitment of mitochondria to olfactory knobs, a mechanism that provides a context-dependent tool for OSNs to maintain cellular homeostasis and signaling integrity.

Publication types

  • Research Support, Non-U.S. Gov't
  • Video-Audio Media

MeSH terms

  • Action Potentials / drug effects
  • Animals
  • Animals, Newborn
  • Calcium / metabolism*
  • Carbonyl Cyanide p-Trifluoromethoxyphenylhydrazone / pharmacology
  • Enzyme Inhibitors / pharmacology
  • Female
  • Fluorescence Recovery After Photobleaching / methods
  • Green Fluorescent Proteins / genetics
  • Green Fluorescent Proteins / metabolism
  • In Vitro Techniques
  • Luminescent Proteins / metabolism
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Microscopy, Electron, Transmission
  • Mitochondria / metabolism*
  • Mitochondria / ultrastructure
  • Olfactory Bulb / cytology
  • Olfactory Receptor Neurons / metabolism
  • Olfactory Receptor Neurons / ultrastructure*
  • Organic Chemicals / pharmacokinetics
  • Patch-Clamp Techniques
  • Proton Ionophores / pharmacology
  • Receptors, Odorant / metabolism
  • Ruthenium Compounds / pharmacology
  • Signal Transduction / drug effects
  • Signal Transduction / physiology*
  • Time Factors
  • Transfection

Substances

  • Enzyme Inhibitors
  • Luminescent Proteins
  • MitoTracker Red 580
  • Organic Chemicals
  • Proton Ionophores
  • Receptors, Odorant
  • Ru 360
  • Ruthenium Compounds
  • Green Fluorescent Proteins
  • Carbonyl Cyanide p-Trifluoromethoxyphenylhydrazone
  • Calcium