title: Mitochondrial Ca(2+) mobilization is a key element in olfactory signaling.
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.
authors.affiliation: Department of Chemosensation, Institute for Biology II, Rheinisch-Westfälische Technische Hochschule Aachen University, Aachen, Germany.
authors.forename: Daniela
authors.initials: D
authors.lastname: Fluegge
authors.forename: Lisa M
authors.initials: LM
authors.lastname: Moeller
authors.forename: Annika
authors.initials: A
authors.lastname: Cichy
authors.forename: Monika
authors.initials: M
authors.lastname: Gorin
authors.forename: Agnes
authors.initials: A
authors.lastname: Weth
authors.forename: Sophie
authors.initials: S
authors.lastname: Veitinger
authors.forename: Silvia
authors.initials: S
authors.lastname: Cainarca
authors.forename: Stefan
authors.initials: S
authors.lastname: Lohmer
authors.forename: Sabrina
authors.initials: S
authors.lastname: Corazza
authors.forename: Eva M
authors.initials: EM
authors.lastname: Neuhaus
authors.forename: Werner
authors.initials: W
authors.lastname: Baumgartner
authors.forename: Jennifer
authors.initials: J
authors.lastname: Spehr
authors.forename: Marc
authors.initials: M
authors.lastname: Spehr
mesh_terms: D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D000831:Animals, Newborn; D002118:Calcium / Q000378:metabolism*; D002259:Carbonyl Cyanide p-Trifluoromethoxyphenylhydrazone / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D036681:Fluorescence Recovery After Photobleaching / Q000379:methods; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D066298:In Vitro Techniques; D008164:Luminescent Proteins / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D046529:Microscopy, Electron, Transmission; D008928:Mitochondria / Q000378:metabolism* / Q000648:ultrastructure; D009830:Olfactory Bulb / Q000166:cytology; D018034:Olfactory Receptor Neurons / Q000378:metabolism / Q000648:ultrastructure*; D009930:Organic Chemicals / Q000493:pharmacokinetics; D018408:Patch-Clamp Techniques; D061209:Proton Ionophores / Q000494:pharmacology; D018035:Receptors, Odorant / Q000378:metabolism; D017975:Ruthenium Compounds / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D013997:Time Factors; D014162:Transfection
chemical_list: D004791:Enzyme Inhibitors; D008164:Luminescent Proteins; C507919:MitoTracker Red 580; D009930:Organic Chemicals; D061209:Proton Ionophores; D018035:Receptors, Odorant; C112020:Ru 360; D017975:Ruthenium Compounds; D049452:Green Fluorescent Proteins; D002259:Carbonyl Cyanide p-Trifluoromethoxyphenylhydrazone; D002118:Calcium