Mitochondrial Distress in Methylmalonic Acidemia: Novel Pathogenic Insights and Therapeutic Perspectives
Mitochondria are highly dynamic, double-membrane-enclosed organelles that sustain cellular metabolism and, hence, cellular, and organismal homeostasis. Dysregulation of the mitochondrial network might, therefore, confer a potentially devastating vulnerability to high-energy-requiring cell types, con...
| Main Authors: | , |
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| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2022-10-01
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| Series: | Cells |
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| Online Access: | https://www.mdpi.com/2073-4409/11/19/3179 |
| _version_ | 1797479908317855744 |
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| author | Svenja Aline Keller Alessandro Luciani |
| author_facet | Svenja Aline Keller Alessandro Luciani |
| author_sort | Svenja Aline Keller |
| collection | DOAJ |
| description | Mitochondria are highly dynamic, double-membrane-enclosed organelles that sustain cellular metabolism and, hence, cellular, and organismal homeostasis. Dysregulation of the mitochondrial network might, therefore, confer a potentially devastating vulnerability to high-energy-requiring cell types, contributing to a broad variety of hereditary and acquired diseases, which include inborn errors of metabolism, cancer, neurodegeneration, and aging-associated adversities. In this Review, we highlight the biological functions of mitochondria-localized enzymes, from the perspective of understanding the pathophysiology of the inherited disorders destroying mitochondrial homeostasis and cellular metabolism. Using methylmalonic acidemia (MMA) as a paradigm of mitochondrial dysfunction, we discuss how mitochondrial-directed signaling pathways sustain the physiological homeostasis of specialized cell types and how these may be disturbed in disease conditions. This Review also provides a critical analysis of molecular underpinnings, through which defects in the autophagy-mediated quality control and surveillance systems contribute to cellular dysfunction, and indicates potential therapeutic strategies for affected tissues. These insights might, ultimately, advance the discovery and development of new therapeutics, not only for methylmalonic acidemia but also for other currently intractable mitochondrial diseases, thus transforming our ability to modulate health and homeostasis. |
| first_indexed | 2024-03-09T21:52:31Z |
| format | Article |
| id | doaj.art-1dee80a6ae22442f8b4858b47b39018e |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-09T21:52:31Z |
| publishDate | 2022-10-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-1dee80a6ae22442f8b4858b47b39018e2023-11-23T20:04:09ZengMDPI AGCells2073-44092022-10-011119317910.3390/cells11193179Mitochondrial Distress in Methylmalonic Acidemia: Novel Pathogenic Insights and Therapeutic PerspectivesSvenja Aline Keller0Alessandro Luciani1Mechanisms of Inherited Kidney Diseases Group, Institute of Physiology, University of Zurich, 8057 Zurich, SwitzerlandMechanisms of Inherited Kidney Diseases Group, Institute of Physiology, University of Zurich, 8057 Zurich, SwitzerlandMitochondria are highly dynamic, double-membrane-enclosed organelles that sustain cellular metabolism and, hence, cellular, and organismal homeostasis. Dysregulation of the mitochondrial network might, therefore, confer a potentially devastating vulnerability to high-energy-requiring cell types, contributing to a broad variety of hereditary and acquired diseases, which include inborn errors of metabolism, cancer, neurodegeneration, and aging-associated adversities. In this Review, we highlight the biological functions of mitochondria-localized enzymes, from the perspective of understanding the pathophysiology of the inherited disorders destroying mitochondrial homeostasis and cellular metabolism. Using methylmalonic acidemia (MMA) as a paradigm of mitochondrial dysfunction, we discuss how mitochondrial-directed signaling pathways sustain the physiological homeostasis of specialized cell types and how these may be disturbed in disease conditions. This Review also provides a critical analysis of molecular underpinnings, through which defects in the autophagy-mediated quality control and surveillance systems contribute to cellular dysfunction, and indicates potential therapeutic strategies for affected tissues. These insights might, ultimately, advance the discovery and development of new therapeutics, not only for methylmalonic acidemia but also for other currently intractable mitochondrial diseases, thus transforming our ability to modulate health and homeostasis.https://www.mdpi.com/2073-4409/11/19/3179epithelial cell distressmetabolismmitochondriamitophagyoxidative stresskidney tubule |
| spellingShingle | Svenja Aline Keller Alessandro Luciani Mitochondrial Distress in Methylmalonic Acidemia: Novel Pathogenic Insights and Therapeutic Perspectives Cells epithelial cell distress metabolism mitochondria mitophagy oxidative stress kidney tubule |
| title | Mitochondrial Distress in Methylmalonic Acidemia: Novel Pathogenic Insights and Therapeutic Perspectives |
| title_full | Mitochondrial Distress in Methylmalonic Acidemia: Novel Pathogenic Insights and Therapeutic Perspectives |
| title_fullStr | Mitochondrial Distress in Methylmalonic Acidemia: Novel Pathogenic Insights and Therapeutic Perspectives |
| title_full_unstemmed | Mitochondrial Distress in Methylmalonic Acidemia: Novel Pathogenic Insights and Therapeutic Perspectives |
| title_short | Mitochondrial Distress in Methylmalonic Acidemia: Novel Pathogenic Insights and Therapeutic Perspectives |
| title_sort | mitochondrial distress in methylmalonic acidemia novel pathogenic insights and therapeutic perspectives |
| topic | epithelial cell distress metabolism mitochondria mitophagy oxidative stress kidney tubule |
| url | https://www.mdpi.com/2073-4409/11/19/3179 |
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