Trypanosome mitochondrial DNA is a network containing thousands of interlocked minicircles. Silencing of a mitochondrial topoisomerase II by RNA interference (RNAi) causes progressive network shrinking, allowing assessment of the minimal network size compatible with viability. We cloned surviving cells after short-term RNAi and found, as expected, that the number of surviving clones decreased with the duration of RNAi. Unexpectedly, a clonal cell line contained heterogeneously sized networks, some being very small. Several experiments showed that cells survived network shrinkage by asymmetrical division of replicated networks, sacrificing daughters with the small progeny network. Therefore, the average network size gradually increased. During the network shrinkage and early stages of recovery, there were changes in the minicircle repertoire.