Autophagy Deficiency by Atg4B Loss Leads to Metabolomic Alterations in Mice
Autophagy is an essential protective mechanism that allows mammalian cells to cope with a variety of stressors and contributes to maintaining cellular and tissue homeostasis. Due to these crucial roles and also to the fact that autophagy malfunction has been described in a wide range of pathologies,...
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| Format: | Article |
| Language: | English |
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MDPI AG
2021-07-01
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| Series: | Metabolites |
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| Online Access: | https://www.mdpi.com/2218-1989/11/8/481 |
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| author | Gemma G. Martínez-García Raúl F. Pérez Álvaro F. Fernández Sylvere Durand Guido Kroemer Guillermo Mariño |
| author_facet | Gemma G. Martínez-García Raúl F. Pérez Álvaro F. Fernández Sylvere Durand Guido Kroemer Guillermo Mariño |
| author_sort | Gemma G. Martínez-García |
| collection | DOAJ |
| description | Autophagy is an essential protective mechanism that allows mammalian cells to cope with a variety of stressors and contributes to maintaining cellular and tissue homeostasis. Due to these crucial roles and also to the fact that autophagy malfunction has been described in a wide range of pathologies, an increasing number of in vivo studies involving animal models targeting autophagy genes have been developed. In mammals, total autophagy inactivation is lethal, and constitutive knockout models lacking effectors of this route are not viable, which has hindered so far the analysis of the consequences of a systemic autophagy decline. Here, we take advantage of <i>atg4b<sup>−/−</sup></i> mice, an autophagy-deficient model with only partial disruption of the process, to assess the effects of systemic reduction of autophagy on the metabolome. We describe for the first time the metabolic footprint of systemic autophagy decline, showing that impaired autophagy results in highly tissue-dependent alterations that are more accentuated in the skeletal muscle and plasma. These changes, which include changes in the levels of amino-acids, lipids, or nucleosides, sometimes resemble those that are frequently described in conditions like aging, obesity, or cardiac damage. We also discuss different hypotheses on how impaired autophagy may affect the metabolism of several tissues in mammals. |
| first_indexed | 2024-03-10T08:35:44Z |
| format | Article |
| id | doaj.art-015476da5adb493da8a96f81f931b7a6 |
| institution | Directory Open Access Journal |
| issn | 2218-1989 |
| language | English |
| last_indexed | 2024-03-10T08:35:44Z |
| publishDate | 2021-07-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Metabolites |
| spelling | doaj.art-015476da5adb493da8a96f81f931b7a62023-11-22T08:38:54ZengMDPI AGMetabolites2218-19892021-07-0111848110.3390/metabo11080481Autophagy Deficiency by Atg4B Loss Leads to Metabolomic Alterations in MiceGemma G. Martínez-García0Raúl F. Pérez1Álvaro F. Fernández2Sylvere Durand3Guido Kroemer4Guillermo Mariño5Departamento de Biología Funcional, Facultad de Medicina, Universidad de Oviedo, 33006 Oviedo, SpainInstituto Universitario de Oncología (IUOPA), 33006 Oviedo, SpainInstituto de Investigación Sanitaria del Principado de Asturias (ISPA), 33011 Oviedo, SpainCentre de Recherche des Cordeliers, INSERM, U1138, F-75006 Paris, FranceCentre de Recherche des Cordeliers, INSERM, U1138, F-75006 Paris, FranceDepartamento de Biología Funcional, Facultad de Medicina, Universidad de Oviedo, 33006 Oviedo, SpainAutophagy is an essential protective mechanism that allows mammalian cells to cope with a variety of stressors and contributes to maintaining cellular and tissue homeostasis. Due to these crucial roles and also to the fact that autophagy malfunction has been described in a wide range of pathologies, an increasing number of in vivo studies involving animal models targeting autophagy genes have been developed. In mammals, total autophagy inactivation is lethal, and constitutive knockout models lacking effectors of this route are not viable, which has hindered so far the analysis of the consequences of a systemic autophagy decline. Here, we take advantage of <i>atg4b<sup>−/−</sup></i> mice, an autophagy-deficient model with only partial disruption of the process, to assess the effects of systemic reduction of autophagy on the metabolome. We describe for the first time the metabolic footprint of systemic autophagy decline, showing that impaired autophagy results in highly tissue-dependent alterations that are more accentuated in the skeletal muscle and plasma. These changes, which include changes in the levels of amino-acids, lipids, or nucleosides, sometimes resemble those that are frequently described in conditions like aging, obesity, or cardiac damage. We also discuss different hypotheses on how impaired autophagy may affect the metabolism of several tissues in mammals.https://www.mdpi.com/2218-1989/11/8/481autophagymetabolomeATG4agingautophagosomeATG8 |
| spellingShingle | Gemma G. Martínez-García Raúl F. Pérez Álvaro F. Fernández Sylvere Durand Guido Kroemer Guillermo Mariño Autophagy Deficiency by Atg4B Loss Leads to Metabolomic Alterations in Mice Metabolites autophagy metabolome ATG4 aging autophagosome ATG8 |
| title | Autophagy Deficiency by Atg4B Loss Leads to Metabolomic Alterations in Mice |
| title_full | Autophagy Deficiency by Atg4B Loss Leads to Metabolomic Alterations in Mice |
| title_fullStr | Autophagy Deficiency by Atg4B Loss Leads to Metabolomic Alterations in Mice |
| title_full_unstemmed | Autophagy Deficiency by Atg4B Loss Leads to Metabolomic Alterations in Mice |
| title_short | Autophagy Deficiency by Atg4B Loss Leads to Metabolomic Alterations in Mice |
| title_sort | autophagy deficiency by atg4b loss leads to metabolomic alterations in mice |
| topic | autophagy metabolome ATG4 aging autophagosome ATG8 |
| url | https://www.mdpi.com/2218-1989/11/8/481 |
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