The mitochondrial life cycle. Since mitochondria cannot be synthesized de novo, they must arise from existing mitochondria. Mitochondrial biogenesis is the process by which mitochondria increase in size, accompanied by lipid synthesis and assembly of ETC subunits. One mitochondrion can divide into two physically distinct mitochondria by the process of fission, which requires the mechanical force of the ER and the Drp1 protein, which is recruited to mitochondria by the Mff receptor. Two mitochondria can also join together to become one mitochondrion with continuous inner- and outer-membranes in a process termed mitochondrial fusion, which requires the proteins Mfn1, Mfn2, and OPA1. In the case of mitochondrial damage, indicated by decreased ETC activity, oxidizing membrane potential, and accumulation of ROS and unfolded proteins, a mitochondrion may be degraded by mitophagy. The marking of mitochondria for degradation is facilitated by the NIX/LC3 pathway during erythrocyte differentiation, and by the Pink1/Parkin pathway in other cell types.