Mitochondrial dysfunction is associated with conditions ranging from severe, inborn errors of metabolism to the very aging process itself. Inherited mitochondrial diseases are rare and tend to be associated with severe defects in the organelle, while aging and age-associated degeneration is universal and tends to be associated with a more subtle, quantitative decline in mitochondrial function. This Keystone conference will address key questions surrounding mitochondrial pathogenesis. Talks will explore the underlying mechanisms and their specificity, looking at whether therapies developed for orphan diseases can be used to treat age associated disorders and vice versa. By bringing together established and emerging rare mitochondrial disease and aging researchers this conference will explore mechanisms of mitochondrial dysfunction across a vast continuum. The ensuing cross-fertilization is expected to result in the synthesis of new testable hypotheses that will help to drive the entire field forward.