Mitochondria-associated protein UQCRH serves as a potential target in mild cognitive impairment of type 1 diabetes mellitus mice.

Type 1 diabetes mellitus (T1DM) and cognitive impairment (CI) are diseases impacting human health. Mild cognitive impairment (MCI), a critical stage of cognitive impairment, is strongly associated with T1DM relating to energy metabolism. Mitochondria, the intracellular energy factories, implicated in diabetic MCI. Therefore, identifying a mitochondrial related biomarker and investigate its role in diabetic MCI are profound. In this study, based on human blood gene datasets obtained from public database, 4 key mitochondrial factors ACADVL, HSPE1, LYPLAL1 and UQCRH were identified by performing differential analysis, functional enrichment analysis and machine learning. To validate these four factors, T1DM mice exhibiting CI and hippocampal damage were observed, UQCRH (a component of mitochondrial complex III) expression reduction was the most obvious amount these four factors in hippocampus, when it was validated in another related dataset. In order to further confirming the role of UQCRH in diabetic MCI, AAV expressing UQCRH intracerebral injection was performed, cognitive impairment of T1DM mice were attenuated post AAV intracerebral injection. Taken together, this study indicated hippocampal mitochondrial dysfunction was involved in diabetic MCI. UQCRH, could be recognized as a biomarker for diabetic MCI, elevating UQCRH expression further improving mitochondrial function served as a potential treatment for diabetic MCI.