The primary cilium and lipophagy translate mechanical forces to direct metabolic adaptation of kidney epithelial cells

Miceli, Caterina; Roccio, Federica; Penalva-Mousset, Lucille; Burtin, Martine; Leroy, Christine; Nemazanyy, Ivan; Kuperwasser, Nicolas; Pontoglio, Marco; Friedlander, Gérard; Morel, Étienne; Terzi, Fabiola; Codogno, Patrice; Dupont, Nicolas

doi:10.1038/s41556-020-0566-0

Cited by 48 publications

(47 citation statements)

References 62 publications

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“…Inhibition or loss of autophagy caused an increase in TAG and LD levels in vitro and in vivo, a decrease in TAG breakdown and a colocalization between ATG components and TAG or LD proteins [83]. Macrolipophagy has subsequently been described in many other mammalian cell types [41,[85][86][87][88][89][90][91][92][93] and it therefore appears that this process contributes ubiquitously to the mobilization of lipids stored in LDs in higher eukaryotes [81].…”

Section: Macrolipophagymentioning

confidence: 99%

The ménage à trois of autophagy, lipid droplets and liver disease

et al. 2021

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Autophagic pathways cross with lipid homeostasis and thus provide energy and essential building blocks that are indispensable for liver functions. Energy deficiencies are compensated by breaking down lipid droplets (LDs), intracellular organelles that store neutral lipids, in part by a selective type of autophagy, referred to as lipophagy. The process of lipophagy does not appear to be properly regulated in fatty liver diseases (FLDs), an important risk factor for the development of hepatocellular carcinomas (HCC). Here we provide an overview on our current knowledge of the biogenesis and functions of LDs, and the mechanisms underlying their lysosomal turnover by autophagic processes. This review also focuses on nonalcoholic steatohepatitis (NASH), a specific type of FLD characterized by steatosis, chronic inflammation and cell death. Particular attention is paid to the role of macroautophagy and macrolipophagy in relation to the parenchymal and non-parenchymal cells of the liver in NASH, as this disease has been associated with inappropriate lipophagy in various cell types of the liver.

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Section: Macrolipophagymentioning

confidence: 99%

The ménage à trois of autophagy, lipid droplets and liver disease

et al. 2021

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“…In addition, another recent report has shown that shear stress caused by fluid flow stimulates lipophagy (selective degradation of lipid droplets by autophagy) in renal epithelial cells in a cilium-dependent manner (54) . It facilitates the production of fatty acids that provide mitochondrial respiratory substrates through β-oxidation to generate ATP.…”

Section: Primary Cilia Regulate Autophagymentioning

confidence: 99%

Autophagy and Ciliogenesis

Yamamoto

Mizushima

2021

JMA J

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Autophagy is a major intracellular degradation system and plays important roles in various physiological processes such as metabolic adaptation and intracellular homeostasis. It degrades intracellular components both randomly and selectively. Autophagic activity is tightly regulated primarily by nutrient availability, but also by other extracellular and intracellular signals. Growing evidence suggests that there are multiple links between autophagy and the primary cilium. The primary cilium is an organelle present on the cell surface and is important for keeping cellular integrity by transducing extracellular stimuli inside the cell. Recent studies have revealed that autophagy selectively degrades the ciliogenesis inhibitory proteins OFD1 and MYH9, promoting ciliogenesis. Conversely, autophagy also inhibits ciliogenesis under growth conditions. The primary cilium can also regulate autophagic activity. These findings suggest that the relationship between autophagy and the primary cilia is bidirectional, and that both are important for maintaining the normal function of various organs.

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“…23 A recent study showed that shear stress originating from urinary ow is sensed by the primary cilia of proximal tubular KECs and stimulates mitochondrial oxidative metabolism via the nutrient-sensing kinase AMPK-PGC1α signaling cascade. 24,25 In the present study, GO and KEGG pathway analysis demonstrated that CFAP45 may play an important role in mitochondrial metabolism via the peroxisome proliferator-activated receptor (PPAR) signaling pathway. In addition, we found that the SMAD4 transcription factor negatively regulates PPARγ coactivator 1α (PGC1α) via the construction of transcriptional regulation network (Table S1).…”

Section: Discussionmentioning

confidence: 64%

CFAP45 is a Potential Predictor of Mitochondrial Dysfunction in Diabetic Kidney Disease

Chen¹,

Shen²,

Shi³

et al. 2021

Preprint

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Background: Cilia and Flagella Associated Protein 45 (CFAP45) is known to be involved in the regulation of ciliary motility. However, its potential role in diabetic kidney disease (DKD) remains unknown. This study demonstrated the role of CFAP45 in the development of DKD based on the Gene Expression Omnibus database.Methods: First, we investigated the expression of CFAP45 in a whole-genome expression microarray (GSE30122). Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis, as well as Gene Set Enrichment Analysis (GSEA), were then conducted to identify the key signaling pathways associated with CFAP45. The networks between transcript factors and hub genes were then constructed by Cytoscape software.Findings: The expression levels of CFAP45 mRNA were reduced in DKD samples as compared to normal samples. Receiver operating characteristic (ROC) curve analysis suggested the significant discriminatory power (area under curve [AUC] = 0.811) of CFAP45 between DKD and normal tissues. Low expression levels of CFAP45 were correlated with apoptosis, senescence and the induction of mast cell infiltration. Function enrichment analysis indicated that CFAP45 is involved in the most significant hallmarks of mitochondrial metabolism dysfunction, including glycolysis and gluconeogenesis, fatty acid metabolism and degradation, ubiquitin-dependent protein catabolic processes, the tricarboxylic acid cycle (TCA) cycle, the action of oxidoreductase on Nicotinamide adenine dinucleotide (NADH), and the peroxisome proliferator-activated receptor (PPAR) signaling pathways located in the mitochondrial matrix and the lysosomal membrane. The transcription factor SMAD4 was found to negatively regulate the PPAR γ coactivator 1α (PGC1α). Interpretation: CFAP45 may regulate mitochondrial metabolic activity by affecting the function of the primary cilium on the kidney epithelial cells. CFAP45 may serve as a potential biomarker for the diagnosis and treatment of DKD.

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The primary cilium and lipophagy translate mechanical forces to direct metabolic adaptation of kidney epithelial cells

Cited by 48 publications

References 62 publications

The ménage à trois of autophagy, lipid droplets and liver disease

The ménage à trois of autophagy, lipid droplets and liver disease

Autophagy and Ciliogenesis

CFAP45 is a Potential Predictor of Mitochondrial Dysfunction in Diabetic Kidney Disease

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The primary cilium and lipophagy translate mechanical forces to direct metabolic adaptation of kidney epithelial cells

Cited by 48 publications

References 62 publications

The ménage à trois of autophagy, lipid droplets and liver disease

The ménage à trois of autophagy, lipid droplets and liver disease

Autophagy and Ciliogenesis

CFAP45 is a&nbsp;Potential Predictor of Mitochondrial Dysfunction in Diabetic Kidney Disease

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CFAP45 is a Potential Predictor of Mitochondrial Dysfunction in Diabetic Kidney Disease