Mitochondrial control of ciliary gene expression and structure in striatal neurons

The Journal of Physiology, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 18, 2025

Abstract Mitochondria play essential metabolic roles and are increasingly understood to interact with other organelles, influencing cellular function disease. Primary cilia, as sensory signalling crucial for neuronal communication function. Emerging evidence suggests that mitochondria primary cilia may regulate processes, recently shown in brain cells such astrocytes. Here, we investigated whether also neurons, focusing on molecular pathways linking both organelles structural components within cilia. We employed a cross‐species, pathway‐focused approach explore connections between mitochondrial ciliary revealing strong associations suggesting coordinated functionality. Furthermore, found viral‐induced downregulation of the fusion gene mitofusin 2 ( Mfn2 ) dopamine D1 receptor‐expressing medium spiny neurons (D1‐MSNs) nucleus accumbens (NAc) altered expression, Crocc – encoding rootletin showing most pronounced downregulation. This reduction expression was linked decreased levels protein, key component rootlet. Notably, viral‐mediated overexpression restored complexity elongation, without compromising adaptation Our findings provide novel functional mitochondria–cilia interaction specifically striatal D1‐MSNs. These results reveal previously unrecognized role dynamics regulating structure potential implications neuropsychiatric neurodegenerative disease mechanisms. image Key points cell structures known producing energy but emerging regulators components, including antenna‐like involved communication. Previous studies suggest influence function, However, this has not been explored neurons. study shows natural variation correlates rats mice. Reducing (Mfn2), protein mitochondria–endoplasmic reticulum interactions, changes specific pathways, notably Crocc, structure, reduces its product, rootletin, which supports integrity. an important highlighting pathway regulation signalling.

Language: Английский

The evolving neurobiology of early-life stress

Neuron, Journal Year: 2025, Volume and Issue: unknown

Published: March 1, 2025

Language: Английский