Cilia bent out of shape over dysfunctional astrocyte mitochondria

Abstract

Mitochondrial dysfunction in astrocytes drives neurodegenerative brain pathology. In this issue, Ignatenko et al. (2022. J. Cell. Biol.https://doi.org/10.1083/jcb.202203019) discover a novel connection between cilia and mitochondria in astrocytes, whereby mitochondrial dysfunction leads to abnormal cilia structure and a motile cilia program.

NEKL-4 regulates microtubule stability and mitochondrial health inC. elegansciliated neurons

“…In different mammalian cell types, mitochondrial stress may promote either ciliogenesis or ciliary degeneration, but in general, increased ciliogenesis improves survival of cells when exposed to ROS (Han et al, 2021; Moruzzi et al, 2022; Ignatenko et al, 2023; Bear and Caspary, 2023; Bae et al, 2023). Cilia stability is influenced in opposing directions by mitochondrial dynamics: mitochondrial fragmentation, which increases ROS, increases ciliogenesis.…”

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“…It has been previously observed in several protocols of hCOs how the aforementioned cell types are generated, differentiated, and migrated radially outward from these proliferative zones, which are composed of neural precursor cells (Lancaster and Knoblich, 2014;Pas › ca et al, 2015). In addition, neurodevelopmental changes have been observed when these regions are altered (Camblor-Perujo and Konon-enko, 2022; Bear and Caspary, 2024).…”

“…The primary cilium has an important role in cortical development and behavior of the RGCs, and its assembly/disassembly is linked to the cell cycle. It seems to play a role in the balance between self-renewal and asymmetric cleavage of RGCs (Bear and Caspary, 2024). Problems in the cilium assembly may be associated with increased proliferation of neural progenitors and macrocephaly, while its disassembly may produce the opposite effect while generating premature differentiation and cell death (Matsumoto et al, 2019).…”

“…Problems in the cilium assembly may be associated with increased proliferation of neural progenitors and macrocephaly, while its disassembly may produce the opposite effect while generating premature differentiation and cell death (Matsumoto et al, 2019). In addition, it has been observed that the primary cilium plays a role as a receptor for signals involved in cell development and differentiation (Yamamoto and Mizushima, 2021;Bear and Caspary, 2024). Clathrin-coated pits in the surrounding ciliary pocket play a role in receptor internalization (Lampe et al, 2016;Camblor-Perujo and Kononenko, 2022).…”