Evidence map›Paper›PMID 41490888›Full record

ArticleCell death discovery2026

Mitochondrial retrograde signaling initiates HIF-1α/BNIP3/NIX-mediated mitophagy in Tibetan high-altitude adaptation.

Yang Wei, Dayan Sun, Fei Wu, Shixuan Zhang, Bowen Cai, Yanyun Ma, Hongxiang Zheng, Xiangguang Shi, Yi Li, Shiguan Le and 3 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cell death discovery, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

3 citing papers in PubMed.

  1. Review
  2. Article
  3. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

13 authors.

Yang Wei *State Key Laboratory of Genetic and Development of Complex Phenotypes, School of Life Sciences & Human Phenome Institute, Fudan University, Shanghai, 200438, China.ORCID http://orcid.org/0009-0003-3709-2949
Dayan Sun *State Key Laboratory of Genetic and Development of Complex Phenotypes, School of Life Sciences & Human Phenome Institute, Fudan University, Shanghai, 200438, China.
Fei Wu *State Key Laboratory of Genetic and Development of Complex Phenotypes, School of Life Sciences & Human Phenome Institute, Fudan University, Shanghai, 200438, China.
Shixuan ZhangState Key Laboratory of Genetic and Development of Complex Phenotypes, School of Life Sciences & Human Phenome Institute, Fudan University, Shanghai, 200438, China.
Bowen CaiState Key Laboratory of Genetic and Development of Complex Phenotypes, School of Life Sciences & Human Phenome Institute, Fudan University, Shanghai, 200438, China.
Yanyun MaAcademy for Engineering & Technology, Fudan University, Shanghai, 200433, China.
Hongxiang ZhengState Key Laboratory of Genetic and Development of Complex Phenotypes, School of Life Sciences & Human Phenome Institute, Fudan University, Shanghai, 200438, China.
Xiangguang ShiState Key Laboratory of Genetic and Development of Complex Phenotypes, School of Life Sciences & Human Phenome Institute, Fudan University, Shanghai, 200438, China.ORCID http://orcid.org/0000-0002-3907-5822
Yi LiState Key Laboratory of Genetic and Development of Complex Phenotypes, School of Life Sciences & Human Phenome Institute, Fudan University, Shanghai, 200438, China.
Shiguan LeState Key Laboratory of Genetic and Development of Complex Phenotypes, School of Life Sciences & Human Phenome Institute, Fudan University, Shanghai, 200438, China.
Xiang ZhouState Key Laboratory of Genetic and Development of Complex Phenotypes, School of Life Sciences & Human Phenome Institute, Fudan University, Shanghai, 200438, China.
Li JinState Key Laboratory of Genetic and Development of Complex Phenotypes, School of Life Sciences & Human Phenome Institute, Fudan University, Shanghai, 200438, China. lijin@fudan.edu.cn.ORCID http://orcid.org/0000-0001-9201-2321
Jiucun WangState Key Laboratory of Genetic and Development of Complex Phenotypes, School of Life Sciences & Human Phenome Institute, Fudan University, Shanghai, 200438, China. jcwang@fudan.edu.cn.ORCID http://orcid.org/0000-0003-2765-0620

Funding

National Natural Science Foundation of China (National Science Foundation of China) U23A20475, 32288101, 82300574, 31871436
6 · The paper itself

Abstract

Genome-wide studies have identified the nuclear gene EPAS1 and the mitochondrial M9a haplogroup as pivotal contributors to hypoxia adaptation in Tibetans. However, the interaction between these two genetic components is not yet clear. In this study, we demonstrate that cells harboring the Tibetan-specific M9a haplogroup with downregulated EPAS1 (M9a+shEPAS1) exhibit enhanced cellular function under hypoxic conditions. These cells display improved mitochondrial function and proliferation, alongside reduced apoptosis and mtDNA-mediated inflammation, driven by the activation of HIF-1α-BNIP3/NIX-mediated mitophagy and an increase in reactive oxygen species (ROS) levels. Furthermore, treatment with N-acetylcysteine (NAC), PX-478, or Mdivi-1 significantly attenuated BNIP3/NIX-mediated mitophagy, leading to an aggravation of mtDNA-mediated inflammation and apoptosis in M9a+shEPAS1 cells during hypoxia. This study first reveals that ROS-driven HIF-1α-BNIP3/NIX-mediated mitophagy mitigates hypoxia-induced inflammation and apoptosis, contributing to the enhanced hypoxia adaptation observed in Tibetans. HIF-1α-BNIP3/NIX-mediated mitophagy may offer potential therapeutic targets for high-altitude illnesses by regulating cellular energy metabolism and inflammation.

Identifiers

PMID41490888
PMCPMC12877009

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.