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FLASH GENE
Symbol LONP1 contributors: mct - updated : 26-01-2017
HGNC name lon peptidase 1, mitochondrial
HGNC id 9479
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
  • three characteristic domains of the Lon A family:
  • a substrate-recognition ‘N’ region,
  • an ATP-binding and hydrolysis region,
  • a serine-proteolytic site
  • a NB-ARC domain, a mitochondrial targeting sequence
  • a LON domain
    • HOMOLOGY
    interspecies homolog to bacterial Lon protease
    homolog to yeast PIM1
    Homologene
    FAMILY
  • PRS protease subfamily S
  • peptidase S16 family
    • CATEGORY enzyme , regulatory
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm,organelle,mitochondria,matrix
    text
  • is a nuclear-encoded gene from chromosome 19 that is transported into mitochondria via a mitochondrial targeting sequence located at the N-terminus
    • basic FUNCTION
  • regulator of mitochondrial DNA replication and for gene expression
  • participates directly in the metabolism of mtDNA
  • required for normal survival and proliferation
  • degrades folded proteins and initiates substrate cleavage non-processively
  • recognizes specific surface determinants or folds, initiates proteolysis at solvent-accessible sites, and generates unfolded polypeptides that are then processively degraded
  • potential roles for LONP1 in linking protein and mtDNA quality control
  • seems to play a major role in the elimination of oxidatively modified proteins in the mitochondrial matrix
  • ATP-powered protease that binds DNA
  • LONP1 and CLPP have been shown to degrade unfolded and damaged proteins in the matrix of mitochondria
  • regulates mitochondrial transcription by stabilizing the mitochondrial TFAM/mtDNA ratio via selective degradation of TFAM
  • modulates mtDNA biogenesis by the selective degradation of TFAM
  • nuclear-encoded mitochondrial enzyme, degrades oxidized proteins of the mitochondrial (mt) matrix, and participates in the replication of mtDNA
  • can be considered a stress responsive protein
  • ATP-dependent protease that controls the selective turnover of mitochondrial matrix proteins
  • nuclearly encoded and mitochondrially located stress-responsive protease, that is involved in heme-mediated ALAS1 turnover
  • has a wide variety of targets and is likely to play different roles depending of the cell type
  • plays a key role in metabolic reprogramming by remodeling OXPHOS complexes and protecting against senescence
  • independent of its proteolytic activity, LONP1 influences function of the mitochondrial genome and respiratory chain
  • importance of mitochondrial Lon (LONP1) in relation to oxidative stress and aging
  • may also contribute, albeit indirectly, to transcriptional regulation within the mitochondria
  • plays an important role in maintaining mitochondrial integrity during aging and aging-related diseases
  • LONP1, LONP2 are in high concentration and close proximity to proteins that are at risk of oxidative damage and have the need for rapid degradation
  • is a nuclear-encoded mitochondrial protease
    • CELLULAR PROCESS protein, degradation
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component
    INTERACTION
    DNA binds a specific sequence in the light and heavy chain promoters of the mitochondrial genome which are involved in regulation of DNA replication and transcription
    RNA
    small molecule nucleotide,
  • ATP dependent
    • protein
  • binds G-quartets through rigid-body binding
  • binds specifically to a single-stranded GT-rich DNA sequence overlapping the light strand promoter of human mitochondrial DNA (mtDNA)
  • in cells with normal mtDNA levels, HMG1-phosphorylated TFAM is degraded by LONP1, but in cells with severe mtDNA deficits, nonphosphorylated TFAM is also degraded, as it is DNA free
  • LONP1 is a target of SIRT3, likely at K917
  • MT-CO2 is a LONP1 substrate
    • cell & other
  • associates with sites distributed primarily within one-half of the genome and preferentially with the control region for mtDNA replication and transcription
    • REGULATION
    Other mitochondrial ATP-dependent
    ASSOCIATED DISORDERS
    corresponding disease(s) CODAS
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral     --over  
    is a poor prognosis marker in human colorectal cancer and melanoma
    Susceptibility to Congenital diaphragmatic hernia (CDH)
    Variant & Polymorphism other
  • CDH probands with LONP1 variants had higher mortality in the neonatal period compared with other children with CDH
    • Candidate gene
    Marker
    Therapy target
    ANIMAL & CELL MODELS
  • inactivation of Lonp1 in mouse embryonic lung epithelium leads to disrupted lung development and full lethality at birth