Identify Key Mitochondrial Autophagy Genes in Schizophrenia through Integrated Bioinformatics Approaches

Kun LIAN; Yongmei LI; Chenglong SHI; Yilan CHEN; Lei ZHANG; Wei YANG; Xiufeng XU

doi:10.12259/j.issn.2095-610X.S20250104

Volume 46 Issue 1

Jan. 2025

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Kun LIAN, Yongmei LI, Chenglong SHI, Yilan CHEN, Lei ZHANG, Wei YANG, Xiufeng XU. Identify Key Mitochondrial Autophagy Genes in Schizophrenia through Integrated Bioinformatics Approaches[J]. Journal of Kunming Medical University, 2025, 46(1): 23-35. doi: 10.12259/j.issn.2095-610X.S20250104

Citation:

Kun LIAN, Yongmei LI, Chenglong SHI, Yilan CHEN, Lei ZHANG, Wei YANG, Xiufeng XU. Identify Key Mitochondrial Autophagy Genes in Schizophrenia through Integrated Bioinformatics Approaches[J]. Journal of Kunming Medical University, 2025, 46(1): 23-35. doi: 10.12259/j.issn.2095-610X.S20250104

Citation:

Kun LIAN, Yongmei LI, Chenglong SHI, Yilan CHEN, Lei ZHANG, Wei YANG, Xiufeng XU. Identify Key Mitochondrial Autophagy Genes in Schizophrenia through Integrated Bioinformatics Approaches[J]. Journal of Kunming Medical University, 2025, 46(1): 23-35. doi: 10.12259/j.issn.2095-610X.S20250104

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Identify Key Mitochondrial Autophagy Genes in Schizophrenia through Integrated Bioinformatics Approaches

doi: 10.12259/j.issn.2095-610X.S20250104

1.
Department of Neurosurgery
2.
Department of Rehabilitation Medicine，The Second Affiliated Hospital of Kunming Medical University，Kunming Yunnan 650101
3.
Department of Psychiatry，The Second People's Hospital of Yuxi/Yuxi Hospital Affiliated to Kunming University of Science and Technology，Yuxi Yunnan 653100
4.
Department of Psychiatry，The First Affiliated Hospital of Kunming Medical University，Kunming Yunnan 650032，China

Received Date: 2024-09-30
Available Online: 2024-12-28
Publish Date: 2025-01-17

Abstract

Abstract

Objective To utilize single-cell and peripheral blood transcriptomic data from 3D brain organoids, combined with machine learning, to analyze the role of mitochondrial autophagy genes in schizophrenia （SCZ）. Methods By integrating two machine learning algorithms, we identified differentially expressed mitochondrial autophagy-related genes between schizophrenia patients and healthy controls using peripheral blood RNA sequencing data. The relationship between mitophagy gene, immune cells and inflammatory factors was further explored. Comprehensive single-cell analysis was used to explore the signaling pathways and specific transcription factors based on mitophagy genes. Results Using machine learning, seven key mitophagy genes expressed in schizophrenia patients were identified. Based on Mitoscore analysis, at the single-cell level, neurons with high mitochondrial autophagy activity （Mitohigh_Neuron） formed new interactions with endothelial cells via the SPP1 signaling pathway. Conclusion This study identified two subtypes of mitophagy and seven key mitophagy genes in schizophrenia, providing new insights into the pathogenesis of the disease.
- Schizophrenia,
- Mitochondrial autophagy,
- Neurons,
- Single-cell sequencing,
- Machine learning

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References(27)

References

[1]	Jauhar S,Johnstone M,McKenna P J. Schizophrenia[J]. Lancet,2022,399(10323):473-486. doi: 10.1016/S0140-6736(21)01730-X
[2]	Sullivan P F,Yao S,Hjerling-Leffler J. Schizophrenia genomics: Genetic complexity and functional insights[J]. Nat Rev Neurosci,2024,25(9):611-624. doi: 10.1038/s41583-024-00837-7
[3]	Momozawa Y,Mizukami K. Unique roles of rare variants in the genetics of complex diseases in humans[J]. J Hum Genet,2021,66(1):11-23. doi: 10.1038/s10038-020-00845-2
[4]	Owen M J,Legge S E,Rees E,et al. Genomic findings in schizophrenia and their implications[J]. Mol Psychiatry,2023,28(9):3638-3647. doi: 10.1038/s41380-023-02293-8
[5]	Roberts R C. Mitochondrial dysfunction in schizophrenia: With a focus on postmortem studies[J]. Mitochondrion,2021,56(1):91-101.
[6]	Ni P,Chung S. Mitochondrial dysfunction in schizophrenia[J]. Bioessays,2020,42(6):e1900202. doi: 10.1002/bies.201900202
[7]	Chen W,Zhao H,Li Y. Mitochondrial dynamics in health and disease: Mechanisms and potential targets[J]. Sig Transduct Target Ther,2023,8(1):333. doi: 10.1038/s41392-023-01547-9
[8]	Di Rienzo M,Romagnoli A,Refolo G,et al. Role of AMBRA1 in mitophagy regulation: Emerging evidence in aging-related diseases[J]. Autophagy,2024,20(12):1-14.
[9]	Roberts R C. Mitochondrial dysfunction in schizophrenia: With a focus on postmortem studies[J]. Mitochondrion,2021,56:91-101. doi: 10.1016/j.mito.2020.11.009
[10]	Andreazza A C,Nierenberg A A. Mitochondrial dysfunction: At the core of psychiatric disorders?[J]. Biol Psychiatry,2018,83(9):718-719. doi: 10.1016/j.biopsych.2018.03.004
[11]	Zhu Y,Zhang J,Deng Q,et al. Mitophagy-associated programmed neuronal death and neuroinflammation[J]. Front Immunol,2024,15(13):1460286.
[12]	Shivakumar V,Rajasekaran A,Subbanna M,et al. Leukocyte mitochondrial DNA copy number in schizophrenia[J]. Asian J Psychiatr,2020,53(89):102193.
[13]	Sebastian R,Song Y,Pak C. Probing the molecular and cellular pathological mechanisms of schizophrenia using human induced pluripotent stem cell models[J]. Schizophr Research,2024,22(1):1-42
[14]	Newman A M,Liu C L,Green M R,et al. Robust enumeration of cell subsets from tissue expression profiles[J]. Nat Methods,2015,12(5):453-457. doi: 10.1038/nmeth.3337
[15]	Zeng D,Ye Z,Shen R,et al. IOBR: Multi-omics immuno-oncology biological research to decode tumor microenvironment and signatures[J]. Frontiers Immunology,2021,12(10):687975.
[16]	Simonsen A T,Hansen M C,Kjeldsen E,et al. Systematic evaluation of signal-to-noise ratio in variant detection from single cell genome multiple displacement amplification and exome sequencing[J]. BMC Genomics,2018,19(1):681. doi: 10.1186/s12864-018-5063-5
[17]	Trigo D,Vit ó ria J J,da Cruz E Silva O A B. Novel therapeutic strategies targeting mitochondria as a gateway in neurodegeneration[J]. Neural Regeneration Research,2023,18(5):991-995. doi: 10.4103/1673-5374.355750
[18]	Zhao Y,Shen W,Zhang M,et al. DDAH-1 maintains endoplasmic reticulum-mitochondria contacts and protects dopaminergic neurons in Parkinson's disease[J]. Cell Death Disease,2024,15(6):399. doi: 10.1038/s41419-024-06772-w
[19]	Ma K,Chen G,Li W,et al. Mitophagy,mitochondrial homeostasis,and cell fate[J]. Front Cell Dev Biol,2020,24(8):467.
[20]	Papageorgiou M P,Filiou M D. Mitochondrial dynamics and psychiatric disorders: The missing link[J]. Neurosci Biobehav Rev,2024,165(10):105837.
[21]	Chen S,Sarasua S M,Davis N J,et al. TOMM40 genetic variants associated with healthy aging and longevity: A systematic review[J]. BMC Geriatr,2022,22(1):667. doi: 10.1186/s12877-022-03337-4
[22]	Choudhury M,Fu T,Amoah K,et al. Widespread RNA hypoediting in schizophrenia and its relevance to mitochondrial function[J]. Sci Adv,2023,9(14):eade9997. doi: 10.1126/sciadv.ade9997
[23]	Bonam S R,Bayry J,Tschan M P,et al. Progress and challenges in the use of MAP1LC3 as a legitimate marker for measuring dynamic autophagy in vivo[J]. Cells,2020,9(5):1321. doi: 10.3390/cells9051321
[24]	Liang M Z,Lu T H,Chen L. Timely expression of PGAM5 and its cleavage control mitochondrial homeostasis during neurite re-growth after traumatic brain injury[J]. Cell Biosci,2023,13(1):96. doi: 10.1186/s13578-023-01052-0
[25]	Cheng M,Lin N,Dong D,et al. PGAM5: A crucial role in mitochondrial dynamics and programmed cell death[J]. Eur J Cell Biol,2021,100(1):151144. doi: 10.1016/j.ejcb.2020.151144
[26]	Lystad A H,Carlsson S R,Simonsen A. Toward the function of mammalian ATG12-ATG5-ATG16L1 complex in autophagy and related processes[J]. Autophagy,2019,5(8):1485-1486.
[27]	Yang K,Yu B,Cheng C,et al. Mir505-3p regulates axonal development via inhibiting the autophagy pathway by targeting ATG12[J]. Autophagy,2017,13(10):1679-1696. doi: 10.1080/15548627.2017.1353841

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