First, we studied the synthetic lethality of mitochondrial pyruvate carrier (MPC) knockout cells. Selective transport of pyruvate across the inner mitochondrial membrane (IMM) by the MPC is a fundamental step that couples cytosolic and mitochondrial metabolism. MPC is unfunctional in many tumors, participating in the metabolic shift that sustains tumorigenesis, and thus represents a potential target for synthetic lethal interventions specific to cancer cells. Here we report the development of cellular models for systematic investigation of both genetic and chemical synthetic lethal partners of MPC. Second, we report for the first time a highly specific expression pattern of a novel placental mammal-specific MPC subunit termed MPC1-like (MPC1L). We show that MPC1L is localized almost exclusively in testis and more specifically in post-meiotic spermatids and sperm cells. This is in marked contrast to MPC1/MPC2 which are ubiquitously expressed throughout the organism.