In contrast to the classical thermodynamic arena of heat engines operating between different temperatures, biological processes are typically assumed to be isothermal, with fluctuations often treated as homogeneous and isotropic. However, recent experimental and theoretical developments have shed light on possible departures from uniform fluctuations. For example, experiments suggest the mitochondrial temperature could be as much as 10K hotter than the rest of the cell [1–4]. This temperature difference could conceivably be accessed by the molecular machine ATP synthase which straddles the mitochondrial membrane. As another example, light-harvesting machines like photosystem II [5] are driven out of equilibrium by solar photons. These light-induced reactions can be treated as coupling to a heat bath at the temperature of the photon source [6–8]. Lastly, the cellular interior supports a host of active fluctuations [9–12] powered by metabolic activity via the motion of large cytosolic components, for example enzymes and related complexes [13, 14] or the cytoskeletal network [15].