The Mitochondrial Protease Lonp1 Maintains Oocyte Development and Survival by Suppressing Nuclear Translocation of AIFM1 in Mammals

Sheng, Xiaoqiang; Liu, Chuan-Ming; Yan, Guijun; Li, Guangyu; Liu, Jingyu; Yang, Yanli; Li, Shiyuan; Li, Zhongxun; Zhou, Jidong; Zhen, Xin; Zhang, Yang; Diao, Zongli; Hu, Yali; Fu, Cuizhang; Yao, Bing; Li, Chao‐Jun; Cao, Yu; Lü, Bin; Yang, Zhongzhou; Qin, Yingying; Sun, Haixiang; Ding, Lijun

doi:10.2139/ssrn.3922637

Cited by 6 publications

(7 citation statements)

References 42 publications

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“…Ovarian samples were removed and fixed in 10% formalin solution at room temperature overnight; dehydrated in 70%, 80%, 90%, 95% and 100% ethanol solutions; and then embedded in paraffin 42 . Sample sections of 5 μm in thickness were deparaffinized and dehydrated with xylene and an ascending series of alcohol solutions.…”

Section: Methodsmentioning

confidence: 99%

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Temporal and spatial dynamics mapping reveals follicle development regulated by different stromal cell populations

Sheng

Zhou

Kang

et al. 2022

Preprint

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Follicle development is a complex dynamic process. The follicles are encapsulated in the stroma, and once the follicle develops, the follicle moves from the cortex to the medulla and finally to the cortex to ovulate in the process of continuous growth. Many of these processes cannot be explained with the follicle alone. Through single-cell and spatial transcriptome sequencing at key time points of follicular development in mice after birth, we found that ovarian stromal cells are not only one of the main cell groups that make up the ovary but that their cell population and spatial location are also closely related to follicular development. Through analysis of cell communication, it was found that ovarian stromal cells were the main transmitters of intercellular communication, and many of the signals they sent were received by granulosa cells and oocytes to participate in follicle development. Ovarian stromal cells are not a homogeneous cell population. We combined single cell types with their spatial location information to divide ovarian stromal cells into four types, namely, structural stromal cells, perifollicular stromal cells, stromal progenitor cells, and steroidogenic stromal cells, each of which plays a different function in follicle development. Indepth studies of the different spatial locations and different types of stromal cells will expand our understanding of follicle development dynamics, leading to new targets and novel approaches for the treatment of ovarian-related diseases.

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Section: Methodsmentioning

confidence: 99%

Section: Immunohistochemistrymentioning

confidence: 99%

Temporal and spatial dynamics mapping reveals follicle development regulated by different stromal cell populations

Sheng

Zhou

Kang

et al. 2022

Preprint

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“…However, Lonp1 loss leads to Aifm1‐mediated apoptosis of oocytes. Similarly, pathogenic LONP1 variants lead to infertility and premature ovarian insufficiency in women (Sheng et al, 2022).…”

Section: Contribution Of Proteases To the Hallmarks Of Agingmentioning

confidence: 99%

Contribution of proteases to the hallmarks of aging and to age‐related neurodegeneration

et al. 2022

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Protein quality control ensures the degradation of damaged and misfolded proteins. Derangement of proteostasis is a primary cause of aging and age‐associated diseases. The ubiquitin–proteasome and autophagy‐lysosome play key roles in proteostasis but, in addition to these systems, the human genome encodes for ~600 proteases, also known as peptidases. Here, we examine the role of proteases in aging and age‐related neurodegeneration. Proteases are present across cell compartments, including the extracellular space, and their substrates encompass cellular constituents, proteins with signaling functions, and misfolded proteins. Proteolytic processing by proteases can lead to changes in the activity and localization of substrates or to their degradation. Proteases cooperate with the autophagy‐lysosome and ubiquitin–proteasome systems but also have independent proteolytic roles that impact all hallmarks of cellular aging. Specifically, proteases regulate mitochondrial function, DNA damage repair, cellular senescence, nutrient sensing, stem cell properties and regeneration, protein quality control and stress responses, and intercellular signaling. The capacity of proteases to regulate cellular functions translates into important roles in preserving tissue homeostasis during aging. Consequently, proteases influence the onset and progression of age‐related pathologies and are important determinants of health span. Specifically, we examine how certain proteases promote the progression of Alzheimer's, Huntington's, and/or Parkinson's disease whereas other proteases protect from neurodegeneration. Mechanistically, cleavage by proteases can lead to the degradation of a pathogenic protein and hence impede disease pathogenesis. Alternatively, proteases can generate substrate byproducts with increased toxicity, which promote disease progression. Altogether, these studies indicate the importance of proteases in aging and age‐related neurodegeneration.

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“…All mice (n=40) had a C57BL/6J genetic background. Chd7 flox/flox (Chd7 f/f ) mice, Chd7-GFP transgenic mice, and Gdf9-Cre mice were obtained as previously described (21,22). Healthy female C57BL/6J mice were maintained as controls.…”

Section: Mice and Genotypingmentioning

confidence: 99%

CHD7 in oocytes is essential for female fertility

Cheng¹,

Dong²,

Lu³

et al. 2022

Ann Transl Med

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Background: Chromodomain helicase DNA-binding protein 7 (CHD7), which is associated with CHARGE (Coloboma, Heart defect, Atresia choanae, Restricted growth, Genital hypoplasia and Ear abnormality) syndrome is an important regulator in many vital developmental processes. However, its role during oocyte development remains unknown. Methods:We screened the Gene Expression Omnibus (GEO) database for expression levels of CHD7 during folliculogenesis. We generated a conditional knockout (cKO) mouse strain with oocyte-specific deletion of CHD7 (Gdf9-Cre:Chd7 f/f ) using the Cre-loxP approach. Evaluation of follicle numbers and reproductive ability was then conducted. In addition, granulosa cell (GC) apoptosis was assessed by terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) assay and cleaved caspase-3, using immunohistochemistry (IHC) and immunofluorescence (IF). GC proliferation was measured by Ki67 staining as evaluated by IHC.Results: In our study, we demonstrated that CHD7 has high expression throughout all developmental stages of the oocyte. We found that deletion of Chd7 in oocytes can cause infertility or sub-fertility in female mice and is associated with decreased follicle numbers at all stages. In addition, we found that GC apoptosis was significantly higher in cKO mice.Conclusions: To our knowledge, our study has been the first to show that CHD7 plays a specific role during oogenesis. Our findings provide new insights into CHD7-related infertility.

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The Mitochondrial Protease Lonp1 Maintains Oocyte Development and Survival by Suppressing Nuclear Translocation of AIFM1 in Mammals

Cited by 6 publications

References 42 publications

Temporal and spatial dynamics mapping reveals follicle development regulated by different stromal cell populations

Temporal and spatial dynamics mapping reveals follicle development regulated by different stromal cell populations

Contribution of proteases to the hallmarks of aging and to age‐related neurodegeneration

CHD7 in oocytes is essential for female fertility

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