Sustaining the strong rhythmic interactions between cellular adaptations and environmental cues has been posited as essential for preserving the physiological and behavioral alignment of an organism to the proper phase of the daily light/dark (LD) cycle. Here, we demonstrate that mitochondria and synaptic input organization of suprachiasmatic (SCN) vasoactive intestinal peptide-expressing (VIP-expressing) neurons showed circadian rhythmicity. Perturbed mitochondrial dynamics achieved by conditional ablation of the fusogenic protein mitofusin 2 (Mfn2) in VIP neurons caused disrupted circadian oscillation in mitochondria and synapses in SCN VIP neurons, leading to desynchronization of entrainment to the LD cycle in Mfn2-deficient mice that resulted in an advanced phase angle of their locomotor activity onset, alterations in core body temperature, and sleep-wake amount and architecture. Our data provide direct evidence of circadian SCN clock machinery dependence on high-performance, Mfn2-regulated mitochondrial dynamics in VIP neurons for maintaining the coherence in daily biological rhythms of the mammalian organism.
Mitofusin 2 controls mitochondrial and synaptic dynamics of suprachiasmatic VIP neurons and related circadian rhythms.
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作者:Stoiljkovic Milan, Song Jae Eun, Hong Hee-Kyung, Endle Heiko, Varela Luis, Catarino Jonatas, Gao Xiao-Bing, Liu Zong-Wu, Sotonyi Peter, Diano Sabrina, Cedernaes Jonathan, Bass Joseph, Horvath Tamas L
期刊: | Journal of Clinical Investigation | 影响因子: | 13.600 |
时间: | 2025 | 起止号: | 2025 Jul 1; 135(13):e185000 |
doi: | 10.1172/JCI185000 |
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