Ciliogenesis is reciprocally regulated by PPARA and NR1H4/FXR through controlling autophagy in vitro and in vivo

Autophagy
Zhi-Qiang LiuRaekil Park

Abstract

The primary cilia are evolutionarily conserved microtubule-based cellular organelles that perceive metabolic status and thus link the sensory system to cellular signaling pathways. Therefore, ciliogenesis is thought to be tightly linked to autophagy, which is also regulated by nutrient-sensing transcription factors, such as PPARA (peroxisome proliferator activated receptor alpha) and NR1H4/FXR (nuclear receptor subfamily 1, group H, member 4). However, the relationship between these factors and ciliogenesis has not been clearly demonstrated. Here, we present direct evidence for the involvement of macroautophagic/autophagic regulators in controlling ciliogenesis. We showed that activation of PPARA facilitated ciliogenesis independently of cellular nutritional states. Importantly, PPARA-induced ciliogenesis was mediated by controlling autophagy, since either pharmacological or genetic inactivation of autophagy significantly repressed ciliogenesis. Moreover, we showed that pharmacological activator of autophagy, rapamycin, recovered repressed ciliogenesis in ppara-/- cells. Conversely, activation of NR1H4 repressed cilia formation, while knockdown of NR1H4 enhanced ciliogenesis by inducing autophagy. The reciprocal activities of P...Continue Reading

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Citations

Aug 25, 2019·Cells·Manuela Morleo, Brunella Franco
Sep 2, 2020·Cells·Prashanta SilwalEun-Kyeong Jo
Nov 30, 2018·Physiological Research·L ŠedováB Bendlová
Mar 20, 2019·International Journal of Molecular Sciences·Lucilla FabbriNathalie M Mazure
May 3, 2019·Biomolecules & Therapeutics·Je Yeong KoJong Hoon Park
Jun 6, 2020·Antioxidants·Ana Martin-HurtadoFrancesc R Garcia-Gonzalo

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Methods Mentioned

BETA
fluorescence microscopy
transmission electron microscopy
transfection
electrophoresis

Software Mentioned

Pro Analyzer
Gel
ImageJ

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