ArticleMolecular metabolism2017
Cdkal1, a type 2 diabetes susceptibility gene, regulates mitochondrial function in adipose tissue.
Article in Molecular metabolism, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers, 1 of them a synthesis that pooled it.
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Who cites it
44 citing papers in PubMed, 1 synthesis or guideline pooled it, 73 citations in OpenAlex.
- Emerging Role of Epitranscriptomics in Diabetes Mellitus and Its Complications.Frontiers in endocrinology · 2022Pooled it
- Germline genome-wide association studies in women receiving neoadjuvant chemotherapy with or without bevacizumab.Pharmacogenetics and genomics · 2018Trial
- Trial
- Associations of maternal CDKAL1 gene with adverse offspring growth patterns.Pediatric research · 2026Article
- Unlocking Ethiopia's genomic landscape and its global significance: a call for inclusive genomics research.Human genomics · 2026Review
- Beer Intake is Positively, While Cheese and Dried Fruit Intake Are Negatively Genetically Correlated with Psoriasis: A GWAS Summary-Statistics Study Using condFDR/conjFDR.Clinical, cosmetic and investigational dermatology · 2026Article
- LONP1 regulation of mitochondrial protein folding provides insight into beta cell failure in type 2 diabetes.Nature metabolism · 2025Article
- Retrograde mitochondrial signaling governs the identity and maturity of metabolic tissues.Science (New York, N.Y.) · 2025Article
- Identification of genetic loci enriched in obese or lean T2D cases in the Korean population.Genes & genomics · 2025Article
- Article
- Understanding the Genetic Landscape of Gestational Diabetes: Insights into the Causes and Consequences of Elevated Glucose Levels in Pregnancy.Metabolites · 2024Review
- Identification and validation of genes associated with prognosis of cisplatin-resistant ovarian cancer.BMC cancer · 2024Article
- Deciphering the Genetic Landscape: Insights Into the Genomic Signatures of Changle Goose.Evolutionary applications · 2024Article
- Analysis of blood methylation quantitative trait loci in East Asians reveals ancestry-specific impacts on complex traits.Nature genetics · 2024Article
- HDL levels modulate the impact of type 2 diabetes susceptibility alleles in older adults.Lipids in health and disease · 2024Article
- Mechanisms and Physiological Roles of Polymorphisms in Gestational Diabetes Mellitus.International journal of molecular sciences · 2024Review
- RNA modifications in physiology and disease: towards clinical applications.Nature reviews. Genetics · 2024Review
- Shared Genetics between Age at Menarche and Type 2 Diabetes Mellitus: Genome-Wide Genetic Correlation Study.Biomedicines · 2024Article
- The Association betweenGenes · 2023Article
- Epitranscriptomics in metabolic disease.Nature metabolism · 2023Review
Corrections and comments
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Authors and funding
16 authors at 5 institutions in 1 country.
Funding
Abstract
objectivesUnderstanding how loci identified by genome wide association studies (GWAS) contribute to pathogenesis requires new mechanistic insights. Variants within CDKAL1 are strongly linked to an increased risk of developing type 2 diabetes and obesity. Investigations in mouse models have focused on the function of Cdkal1 as a tRNA
methodsWe measured mRNA levels of type 2 diabetes GWAS genes, including Cdkal1, in adipose tissue from lean and obese mice. We then established a mouse model with adipocyte-specific Cdkal1 deletion. We examined the effects of adipose Cdkal1 deletion using indirect calorimetry on mice during a cold temperature challenge, as well as by measuring cellular and mitochondrial respiration in vitro. We also examined brown adipose tissue (BAT) mitochondrial morphology by electron microscopy. Utilizing co-immunoprecipitation followed by mass spectrometry, we performed interaction mapping to identify new CDKAL1 binding partners. Furthermore, we tested whether Cdkal1 loss in adipose tissue affects total protein levels or accurate Lys incorporation by tRNA
resultsWe found that Cdkal1 mRNA levels are reduced in adipose tissue of obese mice. Using adipose-specific Cdkal1 KO mice (A-KO), we demonstrated that mitochondrial function is impaired in primary differentiated brown adipocytes and in isolated mitochondria from A-KO brown adipose tissue. A-KO mice displayed decreased energy expenditure during 4 °C cold challenge. Furthermore, mitochondrial morphology was highly abnormal in A-KO BAT. Surprisingly, we found that lysine codon representation was unchanged in Cdkal1 A-KO adipose tissue. We identified novel protein interactors of CDKAL1, including SLC25A4/ANT1, an inner mitochondrial membrane ADP/ATP translocator. ANT proteins can account for the UCP1-independent basal proton leak in BAT mitochondria. Cdkal1 A-KO mice had increased ANT1 protein levels in their white adipose tissue.
conclusionsCdkal1 is necessary for normal mitochondrial morphology and function in adipose tissue. These results suggest that the type 2 diabetes susceptibility gene CDKAL1 has novel functions in regulating mitochondrial activity.
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