Mitoribosome insufficiency in β cells is associated with type 2 diabetes-like islet failure

Hyun Jung Hong, Kyong Hye Joung, Yong Kyung Kim, Min Jeong Choi, Seul Gi Kang, Jung Tae Kim, Yea Eun Kang, Joon Young Chang, Joon Ho Moon, Sangmi Jun, Hyun Joo Ro, Yujeong Lee, Hyeongseok Kim, Jae Hyung Park, Baeki E. Kang, Yunju Jo, Heejung Choi, Dongryeol Ryu, Chul Ho Lee, Hail KimKyu Sang Park, Hyun Jin Kim, Minho Shong

Research output: Contribution to journalArticlepeer-review


Genetic variations in mitoribosomal subunits and mitochondrial transcription factors are related to type 2 diabetes. However, the role of islet mitoribosomes in the development of type 2 diabetes has not been determined. We investigated the effects of the mitoribosomal gene on β-cell function and glucose homeostasis. Mitoribosomal gene expression was analyzed in datasets from the NCBI GEO website (GSE25724, GSE76894, and GSE76895) and the European Nucleotide Archive (ERP017126), which contain the transcriptomes of type 2 diabetic and nondiabetic organ donors. We found deregulation of most mitoribosomal genes in islets from individuals with type 2 diabetes, including partial downregulation of CRIF1. The phenotypes of haploinsufficiency in a single mitoribosomal gene were examined using β-cell-specific Crif1 (Mrpl59) heterozygous-deficient mice. Crif1beta+/− mice had normal glucose tolerance, but their islets showed a loss of first-phase glucose-stimulated insulin secretion. They also showed increased β-cell mass associated with higher expression of Reg family genes. However, Crif1beta+/− mice showed earlier islet failure in response to high-fat feeding, which was exacerbated by aging. Haploinsufficiency of a single mitoribosomal gene predisposes rodents to glucose intolerance, which resembles the early stages of type 2 diabetes in humans.

Original languageEnglish
Pages (from-to)932-945
Number of pages14
JournalExperimental and Molecular Medicine
Issue number7
Publication statusPublished - 2022 Jul

Bibliographical note

Funding Information:
This research was supported by the National Research Foundation of Korea (NRF), funded by the Ministry of Science, ICT & Future Planning (NRF-2017R1E1A1A01075126 and NRF-2020R1A2C2010964), and an MRC Program grant (2017R1A5A2015369).

Publisher Copyright:
© 2022, The Author(s).

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Clinical Biochemistry


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