Cytosolic Quality Control of Mitochondrial Protein Precursors—The Early Stages of the Organelle Biogenesis
With few exceptions, proteins that constitute the proteome of mitochondria originate outside of this organelle in precursor forms. Such protein precursors follow dedicated transportation paths to reach specific parts of mitochondria, where they complete their maturation and perform their functions....
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| Format: | Article |
| Language: | English |
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MDPI AG
2021-12-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/23/1/7 |
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| author | Anna M. Lenkiewicz Magda Krakowczyk Piotr Bragoszewski |
| author_facet | Anna M. Lenkiewicz Magda Krakowczyk Piotr Bragoszewski |
| author_sort | Anna M. Lenkiewicz |
| collection | DOAJ |
| description | With few exceptions, proteins that constitute the proteome of mitochondria originate outside of this organelle in precursor forms. Such protein precursors follow dedicated transportation paths to reach specific parts of mitochondria, where they complete their maturation and perform their functions. Mitochondrial precursor targeting and import pathways are essential to maintain proper mitochondrial function and cell survival, thus are tightly controlled at each stage. Mechanisms that sustain protein homeostasis of the cytosol play a vital role in the quality control of proteins targeted to the organelle. Starting from their synthesis, precursors are constantly chaperoned and guided to reduce the risk of premature folding, erroneous interactions, or protein damage. The ubiquitin-proteasome system provides proteolytic control that is not restricted to defective proteins but also regulates the supply of precursors to the organelle. Recent discoveries provide evidence that stress caused by the mislocalization of mitochondrial proteins may contribute to disease development. Precursors are not only subject to regulation but also modulate cytosolic machinery. Here we provide an overview of the cellular pathways that are involved in precursor maintenance and guidance at the early cytosolic stages of mitochondrial biogenesis. Moreover, we follow the circumstances in which mitochondrial protein import deregulation disturbs the cellular balance, carefully looking for rescue paths that can restore proteostasis. |
| first_indexed | 2024-03-10T03:40:16Z |
| format | Article |
| id | doaj.art-2bcf82e9b71241f384c2ed5443bd918c |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T03:40:16Z |
| publishDate | 2021-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-2bcf82e9b71241f384c2ed5443bd918c2023-11-23T11:33:11ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-12-01231710.3390/ijms23010007Cytosolic Quality Control of Mitochondrial Protein Precursors—The Early Stages of the Organelle BiogenesisAnna M. Lenkiewicz0Magda Krakowczyk1Piotr Bragoszewski2Laboratory of Protein Homeostasis, Nencki Institute of Experimental Biology, Polish Academy of Sciences, 3 Pasteur Street, 02-093 Warsaw, PolandLaboratory of Protein Homeostasis, Nencki Institute of Experimental Biology, Polish Academy of Sciences, 3 Pasteur Street, 02-093 Warsaw, PolandLaboratory of Protein Homeostasis, Nencki Institute of Experimental Biology, Polish Academy of Sciences, 3 Pasteur Street, 02-093 Warsaw, PolandWith few exceptions, proteins that constitute the proteome of mitochondria originate outside of this organelle in precursor forms. Such protein precursors follow dedicated transportation paths to reach specific parts of mitochondria, where they complete their maturation and perform their functions. Mitochondrial precursor targeting and import pathways are essential to maintain proper mitochondrial function and cell survival, thus are tightly controlled at each stage. Mechanisms that sustain protein homeostasis of the cytosol play a vital role in the quality control of proteins targeted to the organelle. Starting from their synthesis, precursors are constantly chaperoned and guided to reduce the risk of premature folding, erroneous interactions, or protein damage. The ubiquitin-proteasome system provides proteolytic control that is not restricted to defective proteins but also regulates the supply of precursors to the organelle. Recent discoveries provide evidence that stress caused by the mislocalization of mitochondrial proteins may contribute to disease development. Precursors are not only subject to regulation but also modulate cytosolic machinery. Here we provide an overview of the cellular pathways that are involved in precursor maintenance and guidance at the early cytosolic stages of mitochondrial biogenesis. Moreover, we follow the circumstances in which mitochondrial protein import deregulation disturbs the cellular balance, carefully looking for rescue paths that can restore proteostasis.https://www.mdpi.com/1422-0067/23/1/7proteostasisprotein precursormitochondrial biogenesisprotein transportprotein degradationmolecular chaperone |
| spellingShingle | Anna M. Lenkiewicz Magda Krakowczyk Piotr Bragoszewski Cytosolic Quality Control of Mitochondrial Protein Precursors—The Early Stages of the Organelle Biogenesis International Journal of Molecular Sciences proteostasis protein precursor mitochondrial biogenesis protein transport protein degradation molecular chaperone |
| title | Cytosolic Quality Control of Mitochondrial Protein Precursors—The Early Stages of the Organelle Biogenesis |
| title_full | Cytosolic Quality Control of Mitochondrial Protein Precursors—The Early Stages of the Organelle Biogenesis |
| title_fullStr | Cytosolic Quality Control of Mitochondrial Protein Precursors—The Early Stages of the Organelle Biogenesis |
| title_full_unstemmed | Cytosolic Quality Control of Mitochondrial Protein Precursors—The Early Stages of the Organelle Biogenesis |
| title_short | Cytosolic Quality Control of Mitochondrial Protein Precursors—The Early Stages of the Organelle Biogenesis |
| title_sort | cytosolic quality control of mitochondrial protein precursors the early stages of the organelle biogenesis |
| topic | proteostasis protein precursor mitochondrial biogenesis protein transport protein degradation molecular chaperone |
| url | https://www.mdpi.com/1422-0067/23/1/7 |
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