Phosphorylation plays a crucial role in the regulation of many fundamental cellular processes. Phosphorylation levels are increased in many cancer cells where they may promote changes in mitochondrial homeostasis. Proteomic studies on various types of cancer identified 17 phosphorylation sites within the human ATP-dependent protease Lon, which degrades misfolded, unassembled and oxidatively damaged proteins in mitochondria. Most of these sites were found in Lon's N-terminal (NTD) and ATPase domains, though little is known about the effects on their function. By combining the biochemical and cryo-electron microscopy studies, we show the effect of Tyr186 and Tyr394 phosphorylations in Lon's NTD, which greatly reduce all Lon activities without affecting its ability to bind substrates or perturbing its tertiary structure. A substantial reduction in Lon's activities is also observed in the presence of polyphosphate, whose amount significantly increases in cancer cells. Our study thus provides an insight into the possible fine-tuning of Lon activities in human diseases, which highlights Lon's importance in maintaining proteostasis in mitochondria.

• MeSH
• Cryoelectron Microscopy MeSH
• Phosphorylation MeSH
• Humans MeSH
• Mitochondria * metabolism   MeSH
• Polyphosphates * metabolism   MeSH
• Protease La * metabolism   MeSH
• Protein Domains MeSH
• Tyrosine * metabolism   MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Names of Substances
• Polyphosphates * MeSH
• Protease La * MeSH
• Tyrosine * MeSH

Acylation modifications, such as the succinylation of lysine, are post-translational modifications and a powerful means of regulating protein activity. Some acylations occur nonenzymatically, driven by an increase in the concentration of acyl group donors. Lysine succinylation has a profound effect on the corresponding site within the protein, as it dramatically changes the charge of the residue. In eukaryotes, it predominantly affects mitochondrial proteins because the donor of succinate, succinyl-CoA, is primarily generated in the tricarboxylic acid cycle. Although numerous succinylated mitochondrial proteins have been identified in Saccharomyces cerevisiae, a more detailed characterization of the yeast mitochondrial succinylome is still lacking. Here, we performed a proteomic MS analysis of purified yeast mitochondria and detected 314 succinylated mitochondrial proteins with 1763 novel succinylation sites. The mitochondrial nucleoid, a complex of mitochondrial DNA and mitochondrial proteins, is one of the structures whose protein components are affected by succinylation. We found that Abf2p, the principal component of mitochondrial nucleoids responsible for compacting mitochondrial DNA in S. cerevisiae, can be succinylated in vivo on at least thirteen lysine residues. Abf2p succinylation in vitro inhibits its DNA-binding activity and reduces its sensitivity to digestion by the ATP-dependent ScLon protease. We conclude that changes in the metabolic state of a cell resulting in an increase in the concentration of tricarboxylic acid intermediates may affect mitochondrial functions.

• Keywords
• DNA–protein interaction, lysine succinylation, mitochondria, mitochondrial DNA, mitochondrial nucleoid, post-translational modification (PTM), proteomics, succinylome, yeast,
• MeSH
• DNA-Binding Proteins genetics   metabolism   MeSH
• Succinic Acid metabolism   MeSH
• Mitochondrial Proteins metabolism   MeSH
• Protein Processing, Post-Translational * MeSH
• Protease La genetics   metabolism   MeSH
• Proteomics * MeSH
• Saccharomyces cerevisiae Proteins genetics   metabolism   MeSH
• Saccharomyces cerevisiae metabolism   MeSH
• Transcription Factors genetics   metabolism   MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Names of Substances
• ABF2 protein, S cerevisiae MeSH Browser
• DNA-Binding Proteins MeSH
• Succinic Acid MeSH
• Mitochondrial Proteins MeSH
• Protease La MeSH
• Saccharomyces cerevisiae Proteins MeSH
• Transcription Factors MeSH

The major role of mitochondria is to provide cells with energy, but no less important are their roles in responding to various stress factors and the metabolic changes and pathological processes that might occur inside and outside the cells. The post-translational modification of proteins is a fast and efficient way for cells to adapt to ever changing conditions. Phosphorylation is a post-translational modification that signals these changes and propagates these signals throughout the whole cell, but it also changes the structure, function and interaction of individual proteins. In this review, we summarize the influence of kinases, the proteins responsible for phosphorylation, on mitochondrial biogenesis under various cellular conditions. We focus on their role in keeping mitochondria fully functional in healthy cells and also on the changes in mitochondrial structure and function that occur in pathological processes arising from the phosphorylation of mitochondrial proteins.

• Keywords
• disease, kinases, mitochondria, phosphorylation,
• Publication type
• Journal Article MeSH
• Review MeSH

Nucleic acid-binding proteins are traditionally divided into two categories: With the ability to bind DNA or RNA. In the light of new knowledge, such categorizing should be overcome because a large proportion of proteins can bind both DNA and RNA. Another even more important features of nucleic acid-binding proteins are so-called sequence or structure specificities. Proteins able to bind nucleic acids in a sequence-specific manner usually contain one or more of the well-defined structural motifs (zinc-fingers, leucine zipper, helix-turn-helix, or helix-loop-helix). In contrast, many proteins do not recognize nucleic acid sequence but rather local DNA or RNA structures (G-quadruplexes, i-motifs, triplexes, cruciforms, left-handed DNA/RNA form, and others). Finally, there are also proteins recognizing both sequence and local structural properties of nucleic acids (e.g., famous tumor suppressor p53). In this mini-review, we aim to summarize current knowledge about the amino acid composition of various types of nucleic acid-binding proteins with a special focus on significant enrichment and/or depletion in each category.

• Keywords
• DNA, G-quadruplex, RNA, Z-DNA, Z-RNA, amino acid composition, cruciform, i-motif, protein binding, triplex,
• MeSH
• DNA-Binding Proteins genetics   MeSH
• DNA genetics   ultrastructure   MeSH
• G-Quadruplexes MeSH
• Nucleic Acid Conformation * MeSH
• Leucine Zippers genetics   MeSH
• Humans MeSH
• Nucleoproteins genetics   ultrastructure   MeSH
• RNA chemistry   ultrastructure   MeSH
• Amino Acid Sequence genetics   MeSH
• Carrier Proteins genetics   ultrastructure   MeSH
• DNA, Z-Form MeSH
• Zinc Fingers genetics   MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Review MeSH
• Names of Substances
• DNA-Binding Proteins MeSH
• DNA MeSH
• Nucleoproteins MeSH
• RNA MeSH
• Carrier Proteins MeSH
• DNA, Z-Form MeSH