Journal of Molecular Medicine

, Volume 94, Issue 12, pp 1373–1384 | Cite as

Fis1 depletion in osteoarthritis impairs chondrocyte survival and peroxisomal and lysosomal function

  • Dongkyun Kim
  • Jinsoo Song
  • Yeonho Kang
  • Sujung Park
  • Yong-Il Kim
  • Seongae Kwak
  • Dongkwon Lim
  • Raekil Park
  • Churl-Hong Chun
  • Seong-Kyu ChoeEmail author
  • Eun-Jung JinEmail author
Original Article


Cumulative evidence suggests the importance of organelle homeostasis in regulating metabolic functions in response to various cellular stresses. Particularly, the dynamism and health of the mitochondria-peroxisome network through fission and fusion are essential for cellular function; dysfunctional dynamism underlies the pathogenesis of several degenerative diseases including Parkinson’s disease. Here, we investigated the role of Fis1 in cartilage homeostasis and its relevance to osteoarthritis (OA). We found that Fis1 is significantly suppressed in human OA chondrocytes compared to that in normal chondrocytes. Fis1 depletion through siRNA induced peroxisomal dysfunction. Moreover, Fis1 suppression altered miRNA profiles, especially those implicated in lysosomal regulation. Lysosomal destruction using LAMP-1-specific targeted nanorods or lysosomal dysfunction through chloroquine treatment resulted in enhanced chondrocyte apoptosis and/or suppression of autophagy. Accordingly, lysosomal activity and autophagy were severely decreased in OA chondrocytes despite abundant LAMP-1-positive organelles. Moreover, Fis1 morpholino-injected zebrafish embryos displayed lysosome accumulation, mitochondrial dysfunction, and peroxisome reduction. Collectively, these data suggest interconnected links among Fis1-modulated miRNA, lysosomes, and autophagy, which contributes to chondrocyte survival/apoptosis. This study represents the first functional study of Fis1 with its pathological relevance to OA. Our data suggest a new target for controlling cartilage-degenerative diseases, such as OA.

Key message

  • Fis1 suppression in OA chondrocytes induces accumulation and inhibition of lysosomes.

  • Fis1 suppression alters miRNAs, especially those implicated in lysosomal regulation.

  • Lysosomal destruction results in chondrocyte apoptosis and suppression of autophagy.

  • Fis1 depletion in zebrafish causes lysosome accumulation, mitochondrial dysfunction, and peroxisome reduction.

  • This is the first functional study of Fis1 and its pathological relevance to OA.


Chondrocytes Osteoarthritis Zebrafish Fis1 Lysosome Mitochondria Peroxisome Apoptosis 



This work was supported by a National Research Foundation of Korea (NRF) grant funded by the Korean government (MSIP) [2013R1A2A2A01067194, 2016R1A2B4010577, 2011-0030130] to E-J Jin and NRF-2014M3A9D8034463 to Choe S-K and Park RK.

Compliance with ethical standards

The study was approved by the institutional review boards (Wonkwang University Ethics Committees, no. WKUH 1519) and performed in compliance with the Helsinki Declaration.

Conflict of interest

The authors declare that they have no competing interests.


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Copyright information

© Springer-Verlag Berlin Heidelberg 2016

Authors and Affiliations

  • Dongkyun Kim
    • 1
  • Jinsoo Song
    • 1
  • Yeonho Kang
    • 1
  • Sujung Park
    • 1
  • Yong-Il Kim
    • 2
  • Seongae Kwak
    • 2
  • Dongkwon Lim
    • 3
  • Raekil Park
    • 2
  • Churl-Hong Chun
    • 4
  • Seong-Kyu Choe
    • 2
    • 5
    Email author
  • Eun-Jung Jin
    • 1
    • 5
    Email author
  1. 1.Department of Biological Sciences, College of Natural SciencesWonkwang UniversityIksanSouth Korea
  2. 2.Department of MicrobiologyWonkwang University School of MedicineIksanSouth Korea
  3. 3.KU-KIST Graduate School of Converging Science and TechnologyKorea UniversitySeoulSouth Korea
  4. 4.Department of Orthopedic SurgeryWonkwang University School of MedicineIksanSouth Korea
  5. 5.Integrated Omics InstituteWonkwang UniversityIksanSouth Korea

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