Archives of Toxicology

, Volume 92, Issue 6, pp 1913–1923 | Cite as

Lon in maintaining mitochondrial and endoplasmic reticulum homeostasis

  • Jieyeqi Yang
  • Wenying Chen
  • Boyang Zhang
  • Fengli Tian
  • Zheng Zhou
  • Xin Liao
  • Chen Li
  • Yi Zhang
  • Yanyan Han
  • Yan Wang
  • Yuzhe Li
  • Guo-Qing Wang
  • Xiao Li ShenEmail author
Review Article


As a vital member of AAA+ (ATPase associated with diverse cellular activities) protein superfamily, Lon, a homo-hexameric ring-shaped protein complex with a serine–lysine catalytic dyad, is highly conserved throughout almost all prokaryotic and eukaryotic organisms. Lon protease (LONP) plays an important role in maintaining mitoproteostasis through selectively recognizing and degrading oxidatively modified mitoproteins within mitochondrial matrix, such as oxidized aconitase, phosphorylated mitochondrial transcription factor A, etc. Furthermore, the up-regulated LONP increased mitochondrial ROS generation to promote cell survival, cell proliferation, epithelial–mesenchymal transition, and cell migration, which was attributed to the up-regulation of NADH:ubiquinone oxidoreductase core subunit S8 via interaction with chaperone Lon under hypoxic or oxidative stress in tumorigenesis. In addition, Lon also participated in protein kinase RNA (PKR)-like endoplasmic reticulum kinase signaling pathway under endoplasmic reticulum (ER) stress. In short, Lon, as a pivotal stress-responsive protein that involved in the crosstalks among mitochondria, ER and nucleus, participated in multifarious important cellular processes crucial for cell survival, such as the mitochondrial protein quality control system, the mitochondrial unfolded protein response, the mtDNA maintenance, and the ER unfolded protein response.


Lon Mitochondrial protein quality control Mitochondrial unfolded protein response mtDNA maintenance Endoplasmic reticulum unfolded protein response Chaperone 



This work was supported by the District Program of National Natural Science Foundation of China (31460426), the Youth Program of National Natural Science Foundation of China (31601577), the Excellent Youth Talents of Zunyi Medical University (17zy-006), the cooperation projects of the Science and Technology Department of Guizhou Province (LH[2014]7546), the projects of Zunyi Science and Technology Bureau (201718), the projects of Zunyi Medical University (ZMKD2013-022) and the supporting discipline construction fund of Zunyi Medical University Ph.D. authorization.

Compliance with ethical standards

Conflict of interest

All authors declare that there are no conflicts of interest.


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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  • Jieyeqi Yang
    • 1
  • Wenying Chen
    • 1
    • 2
  • Boyang Zhang
    • 5
    • 6
  • Fengli Tian
    • 3
  • Zheng Zhou
    • 1
    • 2
  • Xin Liao
    • 1
  • Chen Li
    • 1
  • Yi Zhang
    • 1
    • 2
  • Yanyan Han
    • 1
    • 2
  • Yan Wang
    • 4
  • Yuzhe Li
    • 7
  • Guo-Qing Wang
    • 8
  • Xiao Li Shen
    • 1
    • 2
    Email author
  1. 1.Department of Food Quality and Safety, School of Public HealthZunyi Medical UniversityZunyiPeople’s Republic of China
  2. 2.Experimental Teaching Demonstration Center for Preventive Medicine of Guizhou ProvinceZunyiPeople’s Republic of China
  3. 3.Depatment of OphthalmologyThe Affiliated Hospital of Zunyi Medical UniversityZunyiPeople’s Republic of China
  4. 4.Institute of Food Science and TechnologyChinese Academy of Agricultural SciencesBeijingPeople’s Republic of China
  5. 5.Department of Pharmacology, Perelman School of MedicineUniversity of PennsylvaniaPhiladelphiaUSA
  6. 6.Beijing Advanced Innovation Center for Food Nutrition and Human Health, College of Food Science and Nutritional EngineeringChina Agricultural UniversityBeijingPeople’s Republic of China
  7. 7.China National Center for Food Safety Risk AssessmentBeijingPeople’s Republic of China
  8. 8.Key Laboratory of Basic Pharmacology of Ministry of Education and Joint International Research Laboratory of Ethnomedicine of Ministry of EducationZunyi Medical UniversityZunyiPeople’s Republic of China

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