The extensive and functionally uncharacterized mitochondrial phosphoproteome
| Autor: | Natalie M. Niemi, David J. Pagliarini |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
A-kinase-anchoring protein Pyruvate dehydrogenase kinase Proteome ASBMB Award Article AKAP A-kinase anchoring protein PKL protein kinase-like BCKDK Biology Mitochondrion Biochemistry Mitochondrial Proteins 03 medical and health sciences Phosphoprotein Phosphatases Animals Humans Protein phosphorylation Phosphorylation Protein kinase A Molecular Biology 030102 biochemistry & molecular biology protein phosphatase Phosphoproteomics phosphoproteomics protein kinase Cell Biology BCKDK branched chain amino acid dehydrogenase kinase Phosphoproteins PDH pyruvate dehydrogenase protein phosphorylation Cell biology mitochondria 030104 developmental biology MS mass spectrometry PTM posttranslational modification MTS mitochondrial targeting sequence Protein Kinases PDK pyruvate dehydrogenase kinase |
| Zdroj: | The Journal of Biological Chemistry |
| ISSN: | 0021-9258 |
| DOI: | 10.1016/j.jbc.2021.100880 |
| Popis: | More than half a century ago, reversible protein phosphorylation was linked to mitochondrial metabolism through the regulation of pyruvate dehydrogenase. Since this discovery, the number of identified mitochondrial protein phosphorylation sites has increased by orders of magnitude, driven largely by technological advances in mass spectrometry-based phosphoproteomics. However, the majority of these modifications remain uncharacterized, rendering their function and relevance unclear. Nonetheless, recent studies have shown that disruption of resident mitochondrial protein phosphatases causes substantial metabolic dysfunction across organisms, suggesting that proper management of mitochondrial phosphorylation is vital for organellar and organismal homeostasis. While these data suggest that phosphorylation within mitochondria is of critical importance, significant gaps remain in our knowledge of how these modifications influence organellar function. Here, we curate publicly available datasets to map the extent of protein phosphorylation within mammalian mitochondria and to highlight the known functions of mitochondrial-resident phosphatases. We further propose models by which phosphorylation may affect mitochondrial enzyme activities, protein import and processing, and overall organellar homeostasis. |
| Databáze: | OpenAIRE |
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