2. Academic Validation
  3. DHRS13 suppresses differentiation and mitophagy in glioma via retinoic acid and mitochondrial reactive oxygen species

DHRS13 suppresses differentiation and mitophagy in glioma via retinoic acid and mitochondrial reactive oxygen species

  • Nat Commun. 2025 Jul 30;16(1):6996. doi: 10.1038/s41467-025-62148-4.
Sunyoung Seo # 1,  Min Ji Park # 1,  Min Gi Park # 1,  Minseo Gwak 1,  Yoonji Kim 1,  Junseok Jang 1,  Nayoung Hong 1,  Bok-Sim Lee 2,  Chohee Kim 2,  Seonguk Jo 1,  Hyun Bo Shim 1,  Hyun-Jin Kim 3,  Myung Hun Kim 4,  Seo Hyun Yoo 1,  Seunghyun Yoon 1,  Sua Kim 1,  Jae Hyuk Lee 1,  Sang-Hun Choi 1,  Seon Yong Lee 1,  Gyu-Bum Yeon 1,  Sung-Hye Park 5,  Sung-Hak Kim 3,  Hyunjeong Lee 1 6,  Joo-Yong Lee 4,  Dae-Sung Kim 1,  Byung Cheon Lee 1,  Jong-Whi Park 7,  Hyunggee Kim 8
Affiliations

Affiliations

  • 1 Department of Biotechnology, College of Life Science and Biotechnology, Korea University, Seoul, 02841, Republic of Korea.
  • 2 Department of Life Sciences, Gachon University, Incheon, 21999, Republic of Korea.
  • 3 Department of Animal Science, College of Agriculture and Life Sciences, Chonnam National University, Gwangju, 61186, Republic of Korea.
  • 4 Graduate School of Analytical Science and Technology (GRAST), Chungnam National University, Daejeon, 34133, Republic of Korea.
  • 5 Department of Pathology, Seoul National University Hospital, Seoul, 03082, Republic of Korea.
  • 6 College of Engineering, Institute of Green Manufacturing Research Center, Korea University, Seoul, 02841, Republic of Korea.
  • 7 Department of Life Sciences, Gachon University, Incheon, 21999, Republic of Korea. jpark@gachon.ac.kr.
  • 8 Department of Biotechnology, College of Life Science and Biotechnology, Korea University, Seoul, 02841, Republic of Korea. hg-kim@korea.ac.kr.
  • # Contributed equally.
PMID: 40739132 DOI: 10.1038/s41467-025-62148-4
Abstract

To elucidate the complex interplay of undifferentiated Cancer cells in malignancy, we focus on the crucial mechanisms that maintain the undifferentiated state of Cancer stem-like cells, which drive tumor growth and therapy resistance. Here, we identify a protein called dehydrogenase/reductase 13 (DHRS13) that is abundant in undifferentiated glioblastoma cells. DHRS13 is primarily located in the mitochondria and functions as a retinaldehyde reductase, converting all-trans-retinaldehyde to all-trans-retinol with high affinity for NADPH. Mechanistically, DHRS13 prevents glioma stem-like cells from differentiating by blocking retinoic acid signaling, thereby maintaining their undifferentiated state. Remarkably, the depletion of DHRS13 results in mitochondrial reactive oxygen species-driven Mitophagy and cell death. Consequently, loss of DHRS13 leads to a significant decrease in tumor initiation and progression. These findings hold promise for the development of strategies that target undifferentiated Cancer cells, potentially leading to improved treatment outcomes.

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