Metabolic cues are the main drivers for the differentiation of chloroplasts into chromoplasts and other plastid types.

Plastids show an astounding degree of functional and structural plasticity, ranging from photosynthetic chloroplasts with thylakoids and grana to non-photosynthetic storage organelles such as chromoplasts, which are specialized in the synthesis and sequestration of carotenoid pigments in plastoglobules, crystalline structures, and membrane sacs. Transitions between different plastid types involve extensive rewiring of nuclear gene expression to support the concomitant changes in the proteome and the ultrastructure of plastids. However, the signals triggering the underlying molecular mechanisms are not well understood. In this review, we focus on the chloroplast-to-chromoplast differentiation process in both natural and synthetic (genetically engineered) systems. Using tomato as a model, the review outlines the sequential molecular, structural, and metabolic events driving chromoplastogenesis, including chlorophyll degradation, carotenoid biosynthesis, proteome remodeling, and plastid ultrastructure reorganization. Synthetic systems mimicking this process reveal that sufficient loss of chloroplast identity followed by carotenoid overaccumulation can independently trigger chromoplast formation in plant species and tissues that do not naturally differentiate chromoplasts. These insights highlight metabolic cues as primary drivers of plastid differentiation and adaptation.