Metabolic memory in fruit ripening: bidirectional crosstalk between metabolism and epigenetic regulation

Fruit ripening is a complex developmental process traditionally viewed as being regulated by hormones, transcription factors, and epigenetic modifications in a largely unidirectional manner—with epigenetics acting upstream and metabolism downstream. However, emerging evidence challenges this linear paradigm, revealing that key metabolic intermediates function not merely as outputs of ripening but as critical inputs that shape the epigenetic landscape. This review synthesizes recent advances demonstrating that S-adenosylmethionine (SAM), acetyl-CoA, and NAD + serve as core metabolic “fuels,” with ethylene and polyamines acting as downstream branches and feedback amplifiers within the SAM hub that directly modulate the activity of DNA methyltransferases, histone acetyltransferases, and sirtuin deacetylases, while epigenetic marks may reinforce metabolic states through positive feedback loops. Recent studies have further revealed that metabolic intermediates function as nexus points bridging phytohormone signaling and epigenetic regulation, with SAM, acetyl-CoA, and NAD + serving dual functions in both hormone biosynthesis and epigenetic modifications. We propose that this metabolic–epigenetic bidirectional crosstalk may constitute a “metabolic memory”-like mechanism that contributes to the irreversibility of fruit ripening, rather than providing a fully established explanation. In this review, we operationally define fruit-ripening metabolic memory as a self-reinforcing regulatory state in which metabolic intermediates alter epigenetic marks, and these marks persist beyond the initial metabolic signal and feed back to stabilize metabolic and ripening gene expression programs. Recent transgenic tomato studies engineered to overaccumulate spermidine and spermine provide evidence consistent with this model: metabolic activity was revived even at late developmental stages, with reactivation of cellular programs underlying nitrogen: carbon signaling, energy and glucose metabolism. However, we distinguish direct mechanistic evidence, functional evidence, and correlative evidence throughout the review, and we present the integrated model as a testable framework. By integrating findings from tomato, strawberry, apple, banana, peach, and grape, we present a unified framework in which metabolism and epigenetics operate as an interconnected regulatory network rather than as separate hierarchical layers. We also identify critical knowledge gaps and outline future directions, including the need for real-time metabolic flux analysis coupled with epigenomic profiling, single-cell resolution studies, and exploration of transgenerational inheritance of ripening-related metabolic memory.