Mitochondrial adenosine triphosphate (ATP) synthase is the key enzyme of mitochondrial oxidative phosphorylation reaction.The down-regulation of the mitochondrial ATP synthase is a hallmark of most human carcinomas, which is the embodiment of the bioenergetic signature of cancer in the performance of the decreased oxidative phosphorylation and increased aerobic glycolysis. Combining with the bioenergetic signature of cancer, studies showed that mitochondrial ATP synthase and multidrug resistance and adverse prognosis of tumor were closely related. Its mechanisms are related to post-transcriptional regulation of the ATP synthase,the hypermethylation of the ATP synthase gene and the inhibitor peptide of the mitochondrial ATP synthase, called ATP synthase inhibitory factor 1(IF1). In this review, we stress the biological characteristics of mitochondrial ATP synthase and the relationship between ATP synthase and multidrug resistance and prognosis of Malignant tumor, in order to find a new way for tumor therapy.
The new mechanisms of automaticity controlled by the calcium and membrane clocks in sinoatrial node are helpful to revealing the sinus arrhythmia, but the present calcium dynamic model is only on the single cell level. In the present study, a central and peripheral single cell model was developed, and by exponentially changing the cell membrane capacitance, size, conductance and gap junction from the center to the periphery, a two-dimensional inhomogeneous sinus and atrial model was created on the basis of the anatomical structure. Five-point difference and finite element methods were used to process the internal grids and the borders. Irregular borders were defined by creating segment trial functions. Quantitative experiments suggested the consistency of the central and peripheral action potentials with related reports in amplitude, cycle length, maximum diastolic potential and upstroke velocity. Functions of the calcium and membrane clocks on the leading pacemaker site and upstroke velocity as well as the effects of the atrial premature beat on the sinus automaticity were also in good agreement with those in other studies. The developed model is helpful for deeply studying relative roles of the calcium and membrane clocks in automaticity and the relations with electrical activities in atrium. At the same time it will lay the foundation for building three-dimensional sinus and atrial organic models.