Next Article in Journal
Optimization of Conventional Extraction Parameters for Recovering Phenolic Compounds from Potato (Solanum tuberosum L.) Peels and Their Application as an Antioxidant in Yogurt Formulation
Previous Article in Journal
Upregulation of Thioredoxin Reductase 1 Expression by Flavan-3-Ols Protects Human Kidney Proximal Tubular Cells from Hypoxia-Induced Cell Death
Previous Article in Special Issue
Transcription Factor NRF2 Participates in Cell Cycle Progression at the Level of G1/S and Mitotic Checkpoints
 
 
Article

Loss of KEAP1 Causes an Accumulation of Nondegradative Organelles

1
Departamento de Bioquímica y Biología Molecular y Genética, Facultad de Enfermería y Terapia Ocupacional, Universidad de Extremadura, 10003 Cáceres, Spain
2
Centro de Investigación Biomédica en Red en Enfermedades Neurodegenerativas (CIBERNED), 28029 Madrid, Spain
3
Instituto Universitario de Investigación Biosanitaria de Extremadura (INUBE), 10003 Cáceres, Spain
4
Departamento de Bioquímica, Faculdad de Medicina, Universidad Autónoma de Madrid (UAM), 28049 Madrid, Spain
5
Instituto de Investigaciones Biomédicas Alberto Sols (CSIC-UAM), 28029 Madrid, Spain
6
Instituto de Investigación Sanitaria La Paz (IdiPaz), 28029 Madrid, Spain
*
Authors to whom correspondence should be addressed.
Academic Editor: Young-Sam Keum
Antioxidants 2022, 11(7), 1398; https://doi.org/10.3390/antiox11071398
Received: 24 June 2022 / Revised: 14 July 2022 / Accepted: 15 July 2022 / Published: 19 July 2022
(This article belongs to the Special Issue Transcription Factor Nrf2)
KEAP1 is a cytoplasmic protein that functions as an adaptor for the Cullin-3-based ubiquitin E3 ligase system, which regulates the degradation of many proteins, including NFE2L2/NRF2 and p62/SQSTM1. Loss of KEAP1 leads to an accumulation of protein ubiquitin aggregates and defective autophagy. To better understand the role of KEAP1 in the degradation machinery, we investigated whether Keap1 deficiency affects the endosome-lysosomal pathway. We used KEAP1-deficient mouse embryonic fibroblasts (MEFs) and combined Western blot analysis and fluorescence microscopy with fluorometric and pulse chase assays to analyze the levels of lysosomal-endosomal proteins, lysosomal function, and autophagy activity. We found that the loss of keap1 downregulated the protein levels and activity of the cathepsin D enzyme. Moreover, KEAP1 deficiency caused lysosomal alterations accompanied by an accumulation of autophagosomes. Our study demonstrates that KEAP1 deficiency increases nondegradative lysosomes and identifies a new role for KEAP1 in lysosomal function that may have therapeutic implications. View Full-Text
Keywords: autophagy; cathepsin D; endosomes; KEAP1; LAMP1; lysosomes autophagy; cathepsin D; endosomes; KEAP1; LAMP1; lysosomes
Show Figures

Figure 1

MDPI and ACS Style

Uribe-Carretero, E.; Martinez-Chacón, G.; Yakhine-Diop, S.M.S.; Duque-González, G.; Rodríguez-Arribas, M.; Alegre-Cortés, E.; Paredes-Barquero, M.; Canales-Cortés, S.; Pizarro-Estrella, E.; Cuadrado, A.; González-Polo, R.A.; Fuentes, J.M.; Niso-Santano, M. Loss of KEAP1 Causes an Accumulation of Nondegradative Organelles. Antioxidants 2022, 11, 1398. https://doi.org/10.3390/antiox11071398

AMA Style

Uribe-Carretero E, Martinez-Chacón G, Yakhine-Diop SMS, Duque-González G, Rodríguez-Arribas M, Alegre-Cortés E, Paredes-Barquero M, Canales-Cortés S, Pizarro-Estrella E, Cuadrado A, González-Polo RA, Fuentes JM, Niso-Santano M. Loss of KEAP1 Causes an Accumulation of Nondegradative Organelles. Antioxidants. 2022; 11(7):1398. https://doi.org/10.3390/antiox11071398

Chicago/Turabian Style

Uribe-Carretero, Elisabet, Guadalupe Martinez-Chacón, Sokhna M. S. Yakhine-Diop, Gema Duque-González, Mario Rodríguez-Arribas, Eva Alegre-Cortés, Marta Paredes-Barquero, Saray Canales-Cortés, Elisa Pizarro-Estrella, Antonio Cuadrado, Rosa Ana González-Polo, José M. Fuentes, and Mireia Niso-Santano. 2022. "Loss of KEAP1 Causes an Accumulation of Nondegradative Organelles" Antioxidants 11, no. 7: 1398. https://doi.org/10.3390/antiox11071398

Find Other Styles
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Article Access Map by Country/Region

1
Back to TopTop