Rnd3 Expression is Necessary to Maintain Mitochondrial Homeostasis but Dispensable for Autophagy
Autophagy is a highly conserved process that mediates the targeting and degradation of intracellular components to lysosomes, contributing to the maintenance of cellular homeostasis and to obtaining energy, which ensures viability under stress conditions. Therefore, autophagy defects are common to d...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-06-01
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| Series: | Frontiers in Cell and Developmental Biology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fcell.2022.834561/full |
| _version_ | 1811238974929240064 |
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| author | Cristina Cueto-Ureña Enric Mocholí Josep Escrivá-Fernández Susana González-Granero Sabina Sánchez-Hernández Amalia Solana-Orts Begoña Ballester-Lurbe Karim Benabdellah Rosa M. Guasch José Manuel García-Verdugo Francisco Martín Paul J. Coffer Ignacio Pérez-Roger Enric Poch |
| author_facet | Cristina Cueto-Ureña Enric Mocholí Josep Escrivá-Fernández Susana González-Granero Sabina Sánchez-Hernández Amalia Solana-Orts Begoña Ballester-Lurbe Karim Benabdellah Rosa M. Guasch José Manuel García-Verdugo Francisco Martín Paul J. Coffer Ignacio Pérez-Roger Enric Poch |
| author_sort | Cristina Cueto-Ureña |
| collection | DOAJ |
| description | Autophagy is a highly conserved process that mediates the targeting and degradation of intracellular components to lysosomes, contributing to the maintenance of cellular homeostasis and to obtaining energy, which ensures viability under stress conditions. Therefore, autophagy defects are common to different neurodegenerative disorders. Rnd3 belongs to the family of Rho GTPases, involved in the regulation of actin cytoskeleton dynamics and important in the modulation of cellular processes such as migration and proliferation. Murine models have shown that Rnd3 is relevant for the correct development and function of the Central Nervous System and lack of its expression produces several motor alterations and neural development impairment. However, little is known about the molecular events through which Rnd3 produces these phenotypes. Interestingly we have observed that Rnd3 deficiency correlates with the appearance of autophagy impairment profiles and irregular mitochondria. In this work, we have explored the impact of Rnd3 loss of expression in mitochondrial function and autophagy, using a Rnd3 KO CRISPR cell model. Rnd3 deficient cells show no alterations in autophagy and mitochondria turnover is not impaired. However, Rnd3 KO cells have an altered mitochondria oxidative metabolism, resembling the effect caused by oxidative stress. In fact, lack of Rnd3 expression makes these cells strictly dependent on glycolysis to obtain energy. Altogether, our results demonstrate that Rnd3 is relevant to maintain mitochondria function, suggesting a possible relationship with neurodegenerative diseases. |
| first_indexed | 2024-04-12T12:51:45Z |
| format | Article |
| id | doaj.art-7de0449f54f5452689bd32359d3d685e |
| institution | Directory Open Access Journal |
| issn | 2296-634X |
| language | English |
| last_indexed | 2024-04-12T12:51:45Z |
| publishDate | 2022-06-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Cell and Developmental Biology |
| spelling | doaj.art-7de0449f54f5452689bd32359d3d685e2022-12-22T03:32:27ZengFrontiers Media S.A.Frontiers in Cell and Developmental Biology2296-634X2022-06-011010.3389/fcell.2022.834561834561Rnd3 Expression is Necessary to Maintain Mitochondrial Homeostasis but Dispensable for AutophagyCristina Cueto-Ureña0Enric Mocholí1Josep Escrivá-Fernández2Susana González-Granero3Sabina Sánchez-Hernández4Amalia Solana-Orts5Begoña Ballester-Lurbe6Karim Benabdellah7Rosa M. Guasch8José Manuel García-Verdugo9Francisco Martín10Paul J. Coffer11Ignacio Pérez-Roger12Enric Poch13School of Health Sciences, Universidad CEU Cardenal Herrera, CEU Universities, Valencia, SpainCenter for Molecular Medicine, University Medical Center Utrecht, Utrecht, NetherlandsSchool of Health Sciences, Universidad CEU Cardenal Herrera, CEU Universities, Valencia, SpainLaboratorio de Neurobiologia Comparada, Instituto Cavanilles de Biodiversidad y Biologia Evolutiva, Universidad de Valencia and CIBER de Enfermedades Neurodegenerativas (CIBERNED), Valencia, SpainGenomic Medicine Department, GENYO, Centre for Genomics and Oncological Research, Pfizer-University of Granada-Andalusian Regional Government, Health Sciences Technology Park, Granada, SpainSchool of Health Sciences, Universidad CEU Cardenal Herrera, CEU Universities, Valencia, SpainSchool of Health Sciences, Universidad CEU Cardenal Herrera, CEU Universities, Valencia, SpainGenomic Medicine Department, GENYO, Centre for Genomics and Oncological Research, Pfizer-University of Granada-Andalusian Regional Government, Health Sciences Technology Park, Granada, SpainDepartamento de Bioquímica y Biología Molecular, Facultad de Farmacia, Universidad de Valencia, Valencia, SpainLaboratorio de Neurobiologia Comparada, Instituto Cavanilles de Biodiversidad y Biologia Evolutiva, Universidad de Valencia and CIBER de Enfermedades Neurodegenerativas (CIBERNED), Valencia, SpainGenomic Medicine Department, GENYO, Centre for Genomics and Oncological Research, Pfizer-University of Granada-Andalusian Regional Government, Health Sciences Technology Park, Granada, SpainCenter for Molecular Medicine, University Medical Center Utrecht, Utrecht, NetherlandsSchool of Health Sciences, Universidad CEU Cardenal Herrera, CEU Universities, Valencia, SpainSchool of Health Sciences, Universidad CEU Cardenal Herrera, CEU Universities, Valencia, SpainAutophagy is a highly conserved process that mediates the targeting and degradation of intracellular components to lysosomes, contributing to the maintenance of cellular homeostasis and to obtaining energy, which ensures viability under stress conditions. Therefore, autophagy defects are common to different neurodegenerative disorders. Rnd3 belongs to the family of Rho GTPases, involved in the regulation of actin cytoskeleton dynamics and important in the modulation of cellular processes such as migration and proliferation. Murine models have shown that Rnd3 is relevant for the correct development and function of the Central Nervous System and lack of its expression produces several motor alterations and neural development impairment. However, little is known about the molecular events through which Rnd3 produces these phenotypes. Interestingly we have observed that Rnd3 deficiency correlates with the appearance of autophagy impairment profiles and irregular mitochondria. In this work, we have explored the impact of Rnd3 loss of expression in mitochondrial function and autophagy, using a Rnd3 KO CRISPR cell model. Rnd3 deficient cells show no alterations in autophagy and mitochondria turnover is not impaired. However, Rnd3 KO cells have an altered mitochondria oxidative metabolism, resembling the effect caused by oxidative stress. In fact, lack of Rnd3 expression makes these cells strictly dependent on glycolysis to obtain energy. Altogether, our results demonstrate that Rnd3 is relevant to maintain mitochondria function, suggesting a possible relationship with neurodegenerative diseases.https://www.frontiersin.org/articles/10.3389/fcell.2022.834561/fullRnd3/RhoEneurodisordersmitochondrial dysfunction (MtD)autophagyOXPHOS (oxidative phosphorylation) |
| spellingShingle | Cristina Cueto-Ureña Enric Mocholí Josep Escrivá-Fernández Susana González-Granero Sabina Sánchez-Hernández Amalia Solana-Orts Begoña Ballester-Lurbe Karim Benabdellah Rosa M. Guasch José Manuel García-Verdugo Francisco Martín Paul J. Coffer Ignacio Pérez-Roger Enric Poch Rnd3 Expression is Necessary to Maintain Mitochondrial Homeostasis but Dispensable for Autophagy Frontiers in Cell and Developmental Biology Rnd3/RhoE neurodisorders mitochondrial dysfunction (MtD) autophagy OXPHOS (oxidative phosphorylation) |
| title | Rnd3 Expression is Necessary to Maintain Mitochondrial Homeostasis but Dispensable for Autophagy |
| title_full | Rnd3 Expression is Necessary to Maintain Mitochondrial Homeostasis but Dispensable for Autophagy |
| title_fullStr | Rnd3 Expression is Necessary to Maintain Mitochondrial Homeostasis but Dispensable for Autophagy |
| title_full_unstemmed | Rnd3 Expression is Necessary to Maintain Mitochondrial Homeostasis but Dispensable for Autophagy |
| title_short | Rnd3 Expression is Necessary to Maintain Mitochondrial Homeostasis but Dispensable for Autophagy |
| title_sort | rnd3 expression is necessary to maintain mitochondrial homeostasis but dispensable for autophagy |
| topic | Rnd3/RhoE neurodisorders mitochondrial dysfunction (MtD) autophagy OXPHOS (oxidative phosphorylation) |
| url | https://www.frontiersin.org/articles/10.3389/fcell.2022.834561/full |
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