Synthetic capsules in which a thin membrane encloses some biological or chemical ingredients are used in diverse industrial and biomedical applications. In extreme flow environments, the hydrodynamic loading acting on the membrane of the capsule may cause large deformation and structural failure. Although previous experimental studies have focused on the rheological behavior of capsules immersed in different types of flow, the mechanical characteristics of capsules under high shear rate and their breakup mechanism remain unclear. To investigate the breakup process in a simple shear flow, capsules based on human serum albumin are fabricated and used in experiments with a Couette flow rheoscope. The deformation of a tank-treading capsule is examined with the tension distribution on the membrane estimated by a simple analytical model, and the effects of membrane pre-stress on tension distribution and deformation are analyzed using non-inflated and inflated capsules. A non-inflated capsule without pre-stress continues to elongate with increasing shear rate until breakup, while an inflated capsule with pre-stress exhibits a plateau in the deformation under a high shear rate. Furthermore, based on the measurement of the time scale of breakup, we suggest that the breakup of a capsule may occur as a result of membrane fatigue. Given sufficiently high shear rate, the rupture of a membrane segment is induced by large-amplitude cyclic stress, which leads to the tear-up of the capsule along its meridional plane and finally the formation of two daughter lumps.