LAUSR

Mitochondria are the powerhouses of cells and play important roles in development and health. Besides producing adenosine triphosphate (ATP), mitochondria are also responsible for a number of diverse cellular activities, including reactive oxygen species (ROS) production, calcium signaling, iron homeostasis, steroid synthesis, heme biosynthesis, and programmed cell death (1–3). It is also believed that mitochondria can function as master regulators for immunity and epigenetics (4, 5). Mitochondrial DNA (mtDNA) mutation is one of the major determinants for mitochondrial disorders, which accounts for the vast majority of inborn errors of metabolism with an incidence of 1.6 in 5,000 (6). The advancement of next-generation sequencing techniques enabled us to identify rare variants on both mtDNA and nuclear DNA, and achieved a diagnostic rate of roughly 30%, indicating that mitochondrial diseases may be caused by additional mechanisms (6). In PNAS, Schaefer et al. (7) report a new class of mitochondrial diseases originating from incompatibility between common mtDNA variants, which brings new insights, and complication, for the diagnosis and treatment of mitochondrial diseases.