Quantitative analyses of structure-function heterogeneity of individual mitochondrial components reveal an early role of small-mitochondrial-networks in priming neoplastic transformation

We elucidate a biological mechanism of cancer initiation involving stem cell specification. Based on data from experimentation with a model carcinogen, we propose that conversion of large ‘Hyperfused Mitochondrial Networks’ (HMNs) to heterogenous ‘Small Mitochondrial Networks’ (SMNs) primes non-transformed cells towards stem cell driven neoplasticity. Mechanistically, the SMNs, enriched by modulation of the physical nodes and edges of mitochondrial networks, tunes the mitochondrial redox balance to establish transcriptomic interactions required to maintain a stem cell state to support neoplastic transformation. The scRNAseq data of HaCaT keratinocyte line exposed to model carcinogen TCDD (1nM and 10nM) at the 2.5 hour timepoint