Mitochondria are organelles critical for the functionality of eukaryotic cells. One of their most prominent functions is energy conversion, thereby producing most of the cellular ATP. Energy conversion relies on the oxidative phosphorylation system, an ensemble of large protein complexes that include the respiratory chain and the ATP synthase. Biogenesis of this machinery requires the coordination of two separate genetic systems, namely nuclear and mitochondrial gene expression. Recent research into the molecular causes of aging have revealed a prominent contribution of mitochondrial gene expression on many aspects of degenerative processes that typically involve cellular stress signaling pathways. In this review, we summarize recent developments in attempting to identify the molecular mechanism by which dysfunction of mitochondrial gene expression activates cellular stress signaling pathways and how this affects organismal aging. By comparing data obtained in various model organisms, we identify conserved and species-specific aspects of this mitochondria-to-nucleus signaling.