Role and clinical significance of lymphocyte mitochondrial dysfunction in type 2 diabetes mellitus

Translational Research : the Journal of Laboratory and Clinical Medicine
Saba KhanPradyumna Kumar Mishra

Abstract

Lymphocyte homeostasis in type 2 diabetes mellitus (T2DM) is associated with increased susceptibility to infections. Mitochondrial oxidative stress is implicated primarily in the immune pathophysiology of diabetes; however, the molecular underpinnings of lymphocyte mitochondrial dysfunction and ensuing downstream cellular effects are hitherto unreported. Both in early diagnosed patients and patients with late complications, we observed an inverse correlation between mitochondrial DNA content in lymphocytes and hemoglobin A1 (HbA1c) levels. This relation established for the first time might serve as a general, yet direct, predictor or indicator for mitochondrial dysfunction in T2DM. Compared with controls, nuclear DNA damage response was higher (P ≤ 0.001) in diabetic subjects with increased accumulation of phospho-ataxia-telangiectasia (ATM), γ-H2AX, along with active recruitment of repair proteins (Mre11, Rad50, and Nbs1). A higher frequency (>2%) of stable chromosomal anomalies with loss of telomere integrity was observed in cases with late complications. A significant decrease (P ≤ 0.001) in enzyme activity of complex II, III, and IV of mitochondrial respiratory chain was evident in both diabetic groups in comparison with he...Continue Reading

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Related Concepts

H2AX protein, human
ATM protein, human
Autosome Abnormalities
Diabetes Mellitus, Non-Insulin-Dependent
Genotoxic Stress
Base Excision Repair
DNA Helix Destabilizing Proteins
DNA, Mitochondrial
Histone H7
Communicable Diseases

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