Pyruvate dehydrogenase(PDH)is a multi-enzyme complex in mitochondrion,which plays the crucial function in substance and energy metabolism.PDH catalyzes the decarboxylation of pyruvic acid to produce acetyl coenzyme A,and acetyl coenzyme A serves as the primary raw material to bring the glucose into the aerobic oxidation of tricarboxylic acid cycle(TCA).It has been found that different kinds of PDHA1 mutations cause different kinds of diseases such as lactic acidosis,leigh syndrome,neurological disorders,cerebral palsy and so on.In general,the deficiency of PDH manifests dysfunction caused by the PDHA1 gene mutation.In the present studies,we found that the mutation of PDHA1 resulted in the change PDHA1 conformation,and reduced the enzymatic activity.As compared to wild-type PDHA1,the conformational changes and activity of PDHA1 had obvious difference among a variety of PDHA1 point mutations.Therefore,it is of great significance to study the relationship of structure,function and stability of each mutant.