Age-associated disorders, including neurodegenerative diseases, cancer, and diabetes, impose an enormous global health burden. A common hallmark of these conditions is mitochondrial dysfunction. Mitochondria contain their own genome (mtDNA), which is essential for oxidative phosphorylation but is particularly susceptible to damage and mutation. The progressive accumulation of mtDNA mutations has long been proposed to contribute to ageing and the onset of numerous late-life diseases. Despite this, the molecular mechanisms by which mitochondrial stress is communicated within tissues remain poorly understood. Here, we identify previously unrecognised roles for small non-coding RNAs, including microRNAs (miRNAs) and PIWI-interacting RNAs (piRNAs), in regulating mitochondrial stress signalling. Our work demonstrates that these RNA pathways control both cell-autonomous mitochondrial stress responses and the propagation of mitochondrial stress signals between cells, revealing an unexpected role for small RNAs in coordinating organismal mitochondrial homeostasis.