Mitochondrial Ca2+ mobilization is a key element in olfactory signaling

In olfactory sensory neurons (OSNs), cytosolic Ca2+ controls the gain and sensitivity of olfactory signaling. Important components of the molecular machinery that orchestrates OSN Ca2+ dynamics have been described, but key details are still missing. Here, we demonstrate a critical physiological role of mitochondrial Ca2+ mobilization in mouse OSNs. Combining a new mitochondria! Ca2+ 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 Ca2+ mobilization during sensory stimulation shapes the cytosolic Ca2+ 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.