The thermoacidophile is widely distributed in Yellowstone National Park hot springs that span large gradients in pH (1.60 to 4.84), temperature (42 to 90°C), and mineralogical composition. To characterize the potential role of flexibility in mineral-dependent energy metabolism in contributing to the widespread ecological distribution of this organism, we characterized the spectrum of minerals capable of supporting metabolism and the mechanisms that it uses to access these minerals. The energy metabolism of strain DS80 was supported by elemental sulfur (S), a variety of iron (hydr)oxides, and arsenic sulfide. Strain DS80 reduced, oxidized, and disproportionated S Cells growing via S reduction and disproportionation did not require direct access to the mineral to reduce it, whereas cells growing via S oxidation did require direct access, observations that are attributable to the role of HS produced by S reduction/disproportionation in solubilizing and increasing the bioavailability of S Cells growing via iron (hydr)oxide reduction did not require access to the mineral, suggesting that the cells reduce Fe(III) that is being leached by the acidic growth medium. Cells growing via oxidation of arsenic sulfide with Fe(III) did not require access to the mineral to grow. The stoichiometry of reactants to products indicates that cells oxidize soluble As(III) released from oxidation of arsenic sulfide by aqueous Fe(III). Taken together, these observations underscore the importance of feedbacks between abiotic and biotic reactions in influencing the bioavailability of mineral substrates and defining ecological niches capable of supporting microbial metabolism. Mineral sources of electron donor and acceptor that support microbial metabolism are abundant in the natural environment. However, the spectrum of minerals capable of supporting a given microbial strain and the mechanisms that are used to access these minerals in support of microbial energy metabolism are often unknown, in particular among thermoacidophiles. Here, we show that the thermoacidophile strain DS80 is adapted to use a variety of iron (hydro)oxide minerals, elemental sulfur, and arsenicsulfide to support growth. Cells rely on a complex interplay of abiologically and biologically catalyzed reactions that increase the solubility or bioavailability of minerals, thereby enabling their use in microbial metabolism.