한빛사
>
한빛사논문
한빛사논문
- 조회117
Nat. Commun., 01 December 2025;16,10426(2025) | https://doi.org/10.1038/s41467-025-66460-x
Ei24 deficiency in brown adipocytes induces severe hypothermia under cold stress independent of UCP1 activity
Su Bin Lee1,2,8, Bui Thanh Thu3,4,5,8, Tae Wook Nam1,2, Yaechan Song1, Jae Hoon Lee1,2, Yangsik Jeong3,4,5,6,7 & Han-Woong Lee1,2
1Department of Biochemistry, College of Life Science and Biotechnology, Yonsei University, Seoul, Republic of Korea.
2Gemcro, Inc, Seoul, Republic of Korea.
3Department of Biochemistry, Yonsei University Wonju College of Medicine, Wonju, Republic of Korea.
4Department of Global Medical Science, Yonsei University Wonju College of Medicine, Wonju, Republic of Korea.
5Organelle Medicine Research Center, Wonju College of Medicine, Yonsei University, Wonju, Republic of Korea.
6Institute of Mitochondrial Medicine, Wonju College of Medicine, Yonsei University, Wonju, Republic of Korea.
7ONCOin, Ltd., Chuncheon-si, Gangwon state, Republic of Korea.
8These authors contributed equally: Su Bin Lee, Bui Thanh Thu.
Corresponding authors
Correspondence to Yangsik Jeong or Han-Woong Lee.
1Department of Biochemistry, College of Life Science and Biotechnology, Yonsei University, Seoul, Republic of Korea.
2Gemcro, Inc, Seoul, Republic of Korea.
3Department of Biochemistry, Yonsei University Wonju College of Medicine, Wonju, Republic of Korea.
4Department of Global Medical Science, Yonsei University Wonju College of Medicine, Wonju, Republic of Korea.
5Organelle Medicine Research Center, Wonju College of Medicine, Yonsei University, Wonju, Republic of Korea.
6Institute of Mitochondrial Medicine, Wonju College of Medicine, Yonsei University, Wonju, Republic of Korea.
7ONCOin, Ltd., Chuncheon-si, Gangwon state, Republic of Korea.
8These authors contributed equally: Su Bin Lee, Bui Thanh Thu.
Corresponding authors
Correspondence to Yangsik Jeong or Han-Woong Lee.
Abstract
Brown adipocytes facilitate non-shivering thermogenesis, which is critical for maintaining energy balance and heat production in response to environmental stimuli. Here, we delineate the physiological and biochemical role of etoposide-induced 2.4 (Ei24) in adenosine triphosphate (ATP) production and thermogenesis in brown adipocytes. We generated Ei24 adipocyte-specific knockout (EiaKO) mice that exhibited brown adipose tissue hypertrophy, lipid accumulation, and various mitochondrial abnormalities. Despite mitochondrial defects, uncoupling protein 1 (UCP1) expression and activity remained unchanged. However, those impairments caused lethal hypothermia in mice subjected to cold challenge, underscoring the key role of Ei24 in mitochondrial functions. Mechanistically, Ei24 deficiency disrupted cristae structure, dissipated mitochondrial membrane potential, and reduced matrix pH, leading to severe ATP depletion. We further identify the C-terminal region of Ei24 as essential for supporting ATP synthase function. Those bioenergetic defects not only destabilized the mitochondrial environment necessary for efficient UCP1-mediated thermogenesis, but also impaired ATP-dependent futile cycles such as SERCA-mediated calcium cycling and creatine substrate cycling. Together, our findings indicate that Ei24 functions as a thermogenic regulator that ensures mitochondrial ATP synthesis and structural integrity, enabling both coupled and uncoupled respiration in brown adipose tissue.
논문정보
- Research article
- 2025년 12월 (BRIC 등록일 2025-12-02)
- 국내 연구진
- 생명과학 > 분자생물학
댓글 작성 로그인
팝업 닫기관련 링크
관련분야 논문보기
해당논문 저자보기
