Any feedback?
Please rate this page
(literature.php)
(0/150)

BRENDA support

Literature summary for 3.4.21.53 extracted from

  • Pinti, M.; Gibellini, L.; Nasi, M.; De Biasi, S.; Bortolotti, C.A.; Iannone, A.; Cossarizza, A.
    Emerging role of Lon protease as a master regulator of mitochondrial functions (2016), Biochim. Biophys. Acta, 1857, 1300-1306 .
    View publication on PubMed

Activating Compound

Activating Compound Comment Organism Structure
DNA Escherichia coli Lon binds both single stranded DNA (ssDNA) and RNA (ssRNA), and double stranded DNA (dsDNA) in a non-specific manner, and this interaction enhances Lon ATPase and proteolytic activities Escherichia coli

Crystallization (Commentary)

Crystallization (Comment) Organism
crystal structure determination at 2.0 A resolution Thermococcus onnurineus

Protein Variants

Protein Variants Comment Organism
S855A the Lon mutant, which lacks both ATPase and proteolytic activity, still maintains DNA binding activity but, in this case, does not undergo conformational changes Homo sapiens

Localization

Localization Comment Organism GeneOntology No. Textmining
cell membrane transmembrane enzyme Thermococcus onnurineus
-
-
cytoplasm
-
Escherichia coli 5737
-
mitochondrion
-
Homo sapiens 5739
-
mitochondrion
-
Mus musculus 5739
-
mitochondrion
-
Saccharomyces cerevisiae 5739
-

Natural Substrates/ Products (Substrates)

Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
5-aminolevulinic acid synthase + H2O Homo sapiens
-
?
-
?
cystathionine beta-synthase + H2O Homo sapiens when misfolded or unfolded ?
-
?
cytochrome c oxidase 4 isoform 1 + H2O Homo sapiens i.e. COX4-1 ?
-
?
glutaminase C + H2O Homo sapiens when misfolded or unfolded ?
-
?
mitochondrial aconitase + H2O Homo sapiens when misfolded or unfolded ?
-
?
mitochondrial transcription factor A + H2O Homo sapiens i.e. TFAM ?
-
?
additional information Escherichia coli Escherichia coli Lon binds both single stranded DNA (ssDNA) and RNA (ssRNA), and double stranded DNA (dsDNA) in a non-specific manner, and this interaction enhances Lon ATPase and proteolytic activities ?
-
?
additional information Saccharomyces cerevisiae Lon binding partners are NADH dehydrogenase ubiquinone iron-sulfur protein 8 (NDUFS8), heat shock protein (Hsp)-60, and mtHsp70 ?
-
?
additional information Saccharomyces cerevisiae ATCC 204508 Lon binding partners are NADH dehydrogenase ubiquinone iron-sulfur protein 8 (NDUFS8), heat shock protein (Hsp)-60, and mtHsp70 ?
-
?
steroidogenic acute regulatory protein + H2O Homo sapiens
-
?
-
?

Organism

Organism UniProt Comment Textmining
Escherichia coli P0A9M0
-
-
Homo sapiens P36776
-
-
Mus musculus Q8CGK3
-
-
Saccharomyces cerevisiae P36775
-
-
Saccharomyces cerevisiae ATCC 204508 P36775
-
-
Thermococcus onnurineus B6YU74
-
-

Posttranslational Modification

Posttranslational Modification Comment Organism
acetylation human Lon is target of deacetylase sirtuin 3 (SIRT3), likely at Lys917, which is near the catalytic dyad, thus suggesting that Lon proteolytic activity can be regulated via deacetylation Homo sapiens

Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
5-aminolevulinic acid synthase + H2O
-
Homo sapiens ?
-
?
cystathionine beta-synthase + H2O when misfolded or unfolded Homo sapiens ?
-
?
cytochrome c oxidase 4 isoform 1 + H2O i.e. COX4-1 Homo sapiens ?
-
?
glutaminase C + H2O when misfolded or unfolded Homo sapiens ?
-
?
mitochondrial aconitase + H2O when misfolded or unfolded Homo sapiens ?
-
?
mitochondrial transcription factor A + H2O i.e. TFAM Homo sapiens ?
-
?
additional information Escherichia coli Lon binds both single stranded DNA (ssDNA) and RNA (ssRNA), and double stranded DNA (dsDNA) in a non-specific manner, and this interaction enhances Lon ATPase and proteolytic activities Escherichia coli ?
-
?
additional information Lon binding partners are NADH dehydrogenase ubiquinone iron-sulfur protein 8 (NDUFS8), heat shock protein (Hsp)-60, and mtHsp70 Saccharomyces cerevisiae ?
-
?
additional information Lon efficiency in proteolysis can vary according to the status of its targets Homo sapiens ?
-
?
additional information Lon binding partners are NADH dehydrogenase ubiquinone iron-sulfur protein 8 (NDUFS8), heat shock protein (Hsp)-60, and mtHsp70 Saccharomyces cerevisiae ATCC 204508 ?
-
?
steroidogenic acute regulatory protein + H2O
-
Homo sapiens ?
-
?

Subunits

Subunits Comment Organism
hexamer active enzyme form, modeling of the structure of the human mitochondrial Lon hexamer, overview Homo sapiens
More while proteolytic activity is restricted at the P domain, chaperone activity is mediated by the ATP-binding domain and the N-terminal domain Thermococcus onnurineus

Synonyms

Synonyms Comment Organism
lon protease
-
Homo sapiens
lon protease
-
Thermococcus onnurineus
lon protease
-
Escherichia coli
lon protease
-
Mus musculus
lon protease
-
Saccharomyces cerevisiae
LONP1
-
Homo sapiens
mitochondrial Lon protease
-
Homo sapiens
PIM1
-
Saccharomyces cerevisiae
Protease La
-
Escherichia coli
TonLonB
-
Thermococcus onnurineus

Cofactor

Cofactor Comment Organism Structure
ATP dependent on Homo sapiens
ATP dependent on Thermococcus onnurineus
ATP dependent on Escherichia coli
ATP dependent on Mus musculus
ATP dependent on Saccharomyces cerevisiae

Expression

Organism Comment Expression
Homo sapiens Lon is upregulated after serum starvation up

General Information

General Information Comment Organism
evolution Lon proteases can be divided into two subfamilies: LonA (found in eubacteria and eukarya) and LonB (found in archaea). LonA proteases are formed by three functional domains: the N-terminal, involved in substrate binding, the central AAA+ domain, and the C-terminal domain (named P domain), which containing the Ser-Lys catalytic dyad for proteolytic activity. LonB proteases are composed by an ATPase and a protease domain and a hydrophobic transmembrane region which anchors the protein to the internal face of cell membrane Thermococcus onnurineus
evolution Lon proteases can be divided into two subfamilies: LonA (found in eubacteria and eukarya) and LonB (found in archaea). LonA proteases are formed by three functional domains: the N-terminal, involved in substrate binding, the central AAA+ domain, and the C-terminal domain (named P domain), which containing the Ser-Lys catalytic dyad for proteolytic activity. LonB proteases are composed by an ATPase and a protease domain and a hydrophobic transmembrane region which anchors the protein to the internal face of cell membrane Escherichia coli
evolution Lon proteases can be divided into two subfamilies: LonA (found in eubacteria and eukarya) and LonB (found in archaea). LonA proteases are formed by three functional domains: the N-terminal, involved in substrate binding, the central AAA+ domain, and the C-terminal domain (named P domain), which containing the Ser-Lys catalytic dyad for proteolytic activity. LonB proteases are composed by an ATPase and a protease domain and a hydrophobic transmembrane region which anchors the protein to the internal face of cell membrane. In eukarya, two Lon proteases are present: a mitochondrial and a peroxisomal form, encoded by two different genes Homo sapiens
evolution Lon proteases can be divided into two subfamilies: LonA (found in eubacteria and eukarya) and LonB (found in archaea). LonA proteases are formed by three functional domains: the N-terminal, involved in substrate binding, the central AAA+ domain, and the C-terminal domain (named P domain), which containing the Ser-Lys catalytic dyad for proteolytic activity. LonB proteases are composed by an ATPase and a protease domain and a hydrophobic transmembrane region which anchors the protein to the internal face of cell membrane. In eukarya, two Lon proteases are present: a mitochondrial and a peroxisomal form, encoded by two different genes Mus musculus
evolution Lon proteases can be divided into two subfamilies: LonA (found in eubacteria and eukarya) and LonB (found in archaea). LonA proteases are formed by three functional domains: the N-terminal, involved in substrate binding, the central AAA+ domain, and the C-terminal domain (named P domain), which containing the Ser-Lys catalytic dyad for proteolytic activity. LonB proteases are composed by an ATPase and a protease domain and a hydrophobic transmembrane region which anchors the protein to the internal face of cell membrane. In eukarya, two Lon proteases are present: a mitochondrial and a peroxisomal form, encoded by two different genes Saccharomyces cerevisiae
malfunction downregulation leads to increased starvation-induced autophagy, and accumulation of PTEN-induced putative kinase-1 (PINK1), an essential regulator of mitophagy. Enzyme Lon is involved in genetic diseases and Lon protease plays a crucial role in the process of cell adaptation to a hypoxic environment, overview. Hypoxia leads to Lon upregulation in several cell types in humans, including monocytic acute myelogeneous leukaemia (THP-1), cardiomyocytes, embryonic kidney (293T) cells, rhabdomyosarcoma cells, renal cell carcinoma (RCC4) stably expressing Von Hippel-Lindau protein (VHL) Homo sapiens
malfunction enzyme knockout is embryonically lethal in mice. Lon+/- mouse model, in which the expression of Lon is halved, is characterized by a lower tendency to develop cancer and a higher resistance to carcinogenic compounds than wild type counterparts. Accordingly, growth of Lon-silenced cancer cells in xenograft model is significantly reduced if compared to control cells, while cells overexpressing Lon grow more rapidly. In vivo, Lon overexpression favours glycolysis, facilitates proliferation, and capability to migrate and form metastasis of melanoma cells in nude mice Mus musculus
metabolism functions of Lon protease in human mitochondria, overview. Lon expression highly correlates with expression of heat shock 60 kDa protein-1 (HSPD1), heat shock 10 kDa protein-1 (HSPE1), heat shock 70 kDa protein-9 (HSPA9), and caseinolytic mitochondrial matrix peptidase proteolytic subunit (CLPP), which are all involved in the mitochondrial unfolded protein response (UPRmt) Homo sapiens
additional information the catalytic dyad required for peptide-bond hydrolysis is localized at Ser885-Lys896 Homo sapiens
additional information the enzyme's active site has a Ser-Lys catalytic dyad Escherichia coli
additional information while proteolytic activity is restricted at the P domain, chaperone activity ismediated by the ATP-binding domain and the N-terminal domain. The chaperone and degradation chambers are contiguous and there is virtually no constriction of the chamber between the chaperone domain and the protease active sites Thermococcus onnurineus
physiological function Lon protease (Lonp1) is a nuclear encoded, mitochondrial ATP-dependent serine peptidase, which mediates the selective degradation of mutant and abnormal proteins in the organelle, and helps in the maintenance of mitochondrial homeostasis. Chaperone-like functions of Lon are involved in the assembly of mitochondrial membrane complexes in yeast and in humans, and, at least in yeast, these functions are maintained after inactivation of proteolytic site and are prevented when ATP-binding site is mutated. Together with its proteolytic and chaperone activities, Lon ability to bind DNA is conserved from bacteria to mammalian mitochondria. Lon ability to bind to DNA needs conformational changes in Lon itself, and such changes are inhibited by ATP, and are stimulated by a protein substrate Saccharomyces cerevisiae
physiological function Lon protease (Lonp1) is a nuclear encoded, mitochondrial ATP-dependent serine peptidase, which mediates the selective degradation of mutant and abnormal proteins in the organelle, and helps in the maintenance of mitochondrial homeostasis. In humans, Lon is responsible for the degradation of: 1. stably folded proteins, including 5-aminolevulinic acid synthase, steroidogenic acute regulatory protein and mitochondrial transcription factor A (TFAM) and cytochrome c oxidase 4 isoform 1 (COX4-1), 2. misfolded and unfolded proteins, including glutaminase C, and 3. oxidatively-modified proteins, including mitochondrial aconitase and cystathionine beta-synthase. Lon proteolytic activity plays a role at different stages in the mitochondrial stress response. Chaperone-like functions of Lon are involved in the assembly of mitochondrial membrane complexes in yeast and in humans, and, at least in yeast, these functions are maintained after inactivation of proteolytic site and are prevented when ATP-binding site is mutated. Together with its proteolytic and chaperone activities, Lon ability to bind DNA is conserved from bacteria to mammalian mitochondria. Unlike bacterial Lon, human Lon binds specific ssDNA. Lon ability to bind to DNA needs conformational changes in Lon itself, and such changes are inhibited by ATP, and are stimulated by a protein substrate. By selectively degrading TFAM and controlling TFAM/mtDNA ratio, Lon is responsible for mitochondrial transcription maintenance. Role of Lon protease in carcinogenesis, overview Homo sapiens
physiological function Lon protease (Lonp1) is a nuclear encoded, mitochondrial ATP-dependent serine peptidase, which mediates the selective degradation of mutant and abnormal proteins in the organelle, and helps in the maintenance of mitochondrial homeostasis. Together with its proteolytic and chaperone activities, Lon ability to bind DNA is conserved from bacteria to mammalian mitochondria. Lon ability to bind to DNA needs conformational changes in Lon itself, and such changes are inhibited by ATP, and are stimulated by a protein substrate Mus musculus
physiological function together with its proteolytic and chaperone activities, Lon ability to bind DNA is conserved from bacteria to mammalian mitochondria. Lon ability to bind to DNA needs conformational changes in Lon itself, and such changes are inhibited by ATP, and are stimulated by a protein substrate Thermococcus onnurineus
physiological function together with its proteolytic and chaperone activities, Lon ability to bind mtDNA is conserved from bacteria to mammalian mitochondria. Escherichia coli Lon binds both single stranded DNA (ssDNA) and RNA (ssRNA), and double stranded DNA (dsDNA) in a non-specific manner, and this interaction enhances Lon ATPase and proteolytic activities. Lon ability to bind to DNA needs conformational changes in Lon itself, and such changes are inhibited by ATP, and are stimulated by a protein substrate Escherichia coli