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Updated: Jan 9, 2026
Evaluation of Bioenergetic Function in Cerebral Vascular Endothelial Cells
Published on: November 19, 2016
Mitochondrial biological functions in diverse stroke subtypes: from associations to potential mechanisms
Jing Luo1, Yaling Zheng2, Jialei Chen3
1Department of Pathology, the First Affiliated Hospital of Chongqing Medical University, Chongqing, China; Department of Pathology, Molecular Medicine Diagnostic and Testing Center, Chongqing Medical University, Chongqing, China; Department of Neurology, the First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
Background:
Mitochondrial dysfunction, particularly in energy metabolism, oxidative stress, and apoptosis, has long been implicated in stroke pathogenesis. However, the causal role of specific mitochondrial components remains unclear, especially across distinct stroke subtypes.
Methods:
We performed a bidirectional two-sample Mendelian randomization (MR) analysis using genome-wide association study (GWAS) data for mitochondrial biological functions (N = 15,310) and stroke outcomes from the MEGASTROKE consortium (N = 446,696). Single nucleotide polymorphisms (SNPs) significantly associated with mitochondrial function were selected as instrumental variables. The inverse-variance weighted (IVW) method was used as the primary analysis, with MR-Egger regression, weighted median, and sensitivity analyses applied to assess robustness and pleiotropy.
Results:
The MR analysis identified several mitochondrial proteins with potential causal associations to stroke and its subtypes. Protective factors included MUL1 and NFU1 for any stroke and ETFA for large artery stroke. In contrast, risk factors included TIM14 and AIFM1 for any ischemic stroke, MRPL32 and SLC9B2 for large artery stroke, AIFM1 and HOGA1 for cardioembolic stroke, and SOD2, GRPEL1, and AIFM1 for small vessel stroke. All instrumental variables demonstrated F-statistics >10, and no significant heterogeneity or directional pleiotropy was detected.
Conclusions:
This study provides the first genetic evidence supporting a potential causal role of mitochondrial bioenergetics in stroke risk across subtypes, highlighting subtype-specific metabolic regulators that may hold translational potential for precision prevention and therapy.
