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Peer-Reviewed Publication
Exp Mol Med2026September 2, 2026Journal Article

Oxygen-dependent subcellular redistribution of PHD3 links the hypoxic microenvironment to mitochondrial metabolic reprogramming in ccRCC.

Jaelim Sim1,2, Soyeon Lim2, Changjun Lee2, Hani Jieun Kim3,4, Wonseok Lee1,5, Hyeonki Kim6, Hojun Lee2, Kimyeong Kim2, Mahesh Kumar Teli7, Kyeong Beom Jo8,9, Jacob Wright10, Jee Soo Park11, Myung Eun Lee11, Minsun Jung12, Minsoo Noh1, Dae-Kyum Kim8,9, Mi-Hyun Kim7, Dong Wook Choi5,6, Tae Su Choi1,5, Won Sik Ham13, Hunsang Lee14,15, Haejin Yoon16
1Department of Life Sciences, College of Life Sciences and Biotechnology, Korea University, Seoul, Republic of Korea.
2Department of Biological Sciences, Ulsan National Institute of Science and Technology, Ulsan, Republic of Korea.
3The Kinghorn Cancer Centre and Cancer Research Theme, Garvan Institute of Medical Research, Darlinghurst, New South Wales, Australia.
4St Vincent's Clinical School, Faculty of Medicine, University of New South Wales, Sydney, New South Wales, Australia.
5National Research Laboratory for Convergence Degradation Biology, Korea University, Seoul, South Korea.
6Department of Biotechnology, College of Life Sciences and Biotechnology, Korea University, Seoul, Republic of Korea.
7Gachon Institute of Pharmaceutical Science & Department of Pharmacy, College of Pharmacy, Gachon University, Incheon, Republic of Korea.
8Division of Thoracic and Upper Gastrointestinal Surgery, Department of Surgery, Faculty of Medicine and Health Sciences, McGill University, Montreal, Quebec, Canada.
9Cancer Research Program, Research Institute of McGill University Health Centre, Montreal, Quebec, Canada.
10Department of Cancer Genetics and Genomics, Roswell Park Comprehensive Cancer Center, Buffalo, NY, USA.
11Department of Urology and Urological Science Institute, Yonsei University College of Medicine, Seoul, Republic of Korea.
12Department of Pathology, Yonsei University College of Medicine, Seoul, Republic of Korea.
13Department of Urology and Urological Science Institute, Yonsei University College of Medicine, Seoul, Republic of Korea. UROHAM@yuhs.ac.
14Department of Life Sciences, College of Life Sciences and Biotechnology, Korea University, Seoul, Republic of Korea. hunsang@korea.ac.kr.
15National Research Laboratory for Convergence Degradation Biology, Korea University, Seoul, South Korea. hunsang@korea.ac.kr.
16Department of Biological Sciences, Ulsan National Institute of Science and Technology, Ulsan, Republic of Korea. haejinyoon@unist.ac.kr.
PubMed DOI

Abstract

Clear cell renal cell carcinoma (ccRCC) is characterized by profound metabolic dysregulation, with both prolyl hydroxylase domain protein 3 (PHD3) and pyruvate carboxylase (PC) independently implicated in disease progression. Although each influences patient outcomes, a direct mechanistic interplay between these two regulators has remained elusive. Here, we uncover a novel regulatory axis involvin…

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