Mitochondrial impairment and intracellular reactive oxygen species alter primary cilia morphology

Abstract

Primary cilia have recently emerged as cellular signaling organelles. Their homeostasis and function require a high amount of energy. However, how energy depletion and mitochondria impairment affect cilia have barely been addressed. We first studied the spatial relationship between a mitochondria subset in proximity to the cilium in vitro, finding similar mitochondrial activity measured as mitochondrial membrane potential compared with the cellular network. Next, using common primary cilia cell models and inhibitors of mitochondrial energy production, we found alterations in cilia number and/or length due to energy depletion and mitochondrial reactive oxygen species (ROS) overproduction. Finally, by using a mouse model of type 2 diabetes mellitus, we provided in vivo evidence that cilia morphology is impaired in diabetic nephropathy, which is characterized by ROS overproduction and impaired mitochondrial metabolism. In conclusion, we showed that energy imbalance and mitochondrial ROS affect cilia morphology and number, indicating that conditions characterized by mitochondria and radicals imbalances might lead to ciliary impairment.

Icariin Treatment Rescues Diabetes Induced Bone Loss via Scavenging ROS and Activating Primary Cilia/Gli2/Osteocalcin Signaling Pathway

“…At the same time, we used Mito Tempo, a proven mitochondrion-specific scavenger of ROS, as a drug control, the results showed that ICA had a similar inhibitory effect on ROS as Mito Tempo ( Figure 6 H). More recently, Moruzzi et al have shown that primary cilia damaged is the result of diabetes induced ROS excess and impaired mitochondrial metabolism [ 48 ]. These results suggest that ICA can rescue osteoblast differentiation under a high glucose environment because it inhibits ROS to maintain the functional homeostasis of mitochondria and primary cilia.…”

“…Our primary focus is on the role ROS plays in diabetic bone loss, and a large number of studies suggested that the main factors were that ROS promoted lipid peroxidation, reduced antioxidants, promoted bone resorption, and induced osteoblast apoptosis [ 65 ]. In addition, recent studies have confirmed that a lack of mitochondrial energy and ROS overproduction lead to cilia loss in diabetic nephropathy [ 48 ]. Ji et al found that deletion of Prdx5, an antioxidant enzyme, could lead to abnormal ciliogenesis due to excess ROS [ 62 ], while decreased expression of several Prdx proteins was found in HFD-induced insulin resistance model mice [ 66 ].…”

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.…”

Ciliated, Mitochondria-Rich Postmitotic Cells are Immune-privileged, and Mimic Immunosuppressive Microenvironment of Tumor-Initiating Stem Cells: From Molecular Anatomy to Molecular Pathway

“…It has been demonstrated that mitochondrial dysfunction and ROS accumulation can decrease cilia number and/or length in the inner medullary collecting duct cells. In addition, mitochondrial dysfunction can lead to ciliary dysfunction by reducing cellular adenosine triphosphate (ATP) content [121]. In support, Ignatenko et al [122] found similar findings in astrocytes.…”