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Study overview. We analyzed nine single-cell cancer datasets [4, 21, 22, 23, 24, 25, 26, 27, 28] across 134 patients and 420,747 cells from various cancer types, categorizing cells by their percentage of mitochondrial-encoded gene RNA counts (pctMT), with cells above 15% designated as high mitochondrial content cells (HighMT). First, we examined potential links between pctMT and common artifacts, including dissociation-induced stress. We then confirmed regions of high-density malignant HighMT cells in Visium HD slides and explored metabolic dysregulation, notably an increase in xenobiotic metabolism in malignant HighMT cells. We linked cell line pctMT levels to differential drug resistance and sensitivity. Finally, we identified significant associations between pctMT and established cancer cell states, along with key clinical characteristics

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