Mitochondrial DNA (mtDNA) is organized in nucleoids in complex with accessory 
proteins, proteins of mtDNA replication and gene expression machinery. A robust 
mtDNA genome is represented by hundreds to thousands of nucleoids in cell 
mitochondrion. Detailed information is lacking about the dynamics of nucleoid 
distribution within the mitochondrial network upon physiological and 
pathological events. Therefore, we used confocal microscopy to study 
mitochondrial nucleoid redistribution upon mitochondrial fission and following 
reintegration of the mitochondrial network. Fission was induced by oxidative 
stress at respiration inhibition by rotenone or upon elimination of the 
protonmotive force by uncoupling or upon canceling its electrical component, 
ΔΨ(m), by valinomycin; and by silencing of mitofusin MFN2. Agent withdrawal 
resulted in concomitant mitochondrial network reintegration. We found two major 
principal morphological states: (i) a tubular state of the mitochondrial network 
with equidistant nucleoid spacing, 1.10±0.2 nucleoids per μm, and (ii) a 
fragmented state of solitary spheroid objects in which several nucleoids were 
clustered. We rarely observed singular mitochondrial fragments with a single 
nucleoid inside and very seldom we observed empty fragments. Reintegration of 
fragments into the mitochondrial network re-established the tubular state with 
equidistant nucleoid spacing. The two major morphological states coexisted at 
intermediate stages. These observations suggest that both mitochondrial network 
fission and reconnection of the disintegrated network are nucleoid-centric, 
i.e., fission and new mitochondrial tubule formation are initiated around 
nucleoids. Analyses of combinations of these morphological icons thus provide a 
basis for a future mitochondrial morphology diagnostics.