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Abstract The inner mitochondrial membrane (IMM) is a densely packed bioenergetic surface where electron transfer, proton pumping , and ATP synthesis are tightly coupled, and where performance is shaped by membrane leak , lipid composition, and higher-order organization. Although experimental reconstruction of oxidative phosphorylation in proteoliposomes has advanced, systematic exploration of design tradeoffs remains challenging because key parameters covary across preparations. Here we present a fully reproducible computational synthetic IMM (syn-IMM) framework that models coupled membrane energization and ATP production, then uses structured perturbations, parameter sweeps, and sensitivity analyses to identify dominant control variables. In a Δψ-proxy simulator, we show that ATP output is maximized within a narrow cardiolipin performance window (peak at cardiolipin fraction 0.18 in our benchmarked parameterization), while increasing leak globally suppresses performance, producing a cardiolipin × leak landscape in which coupling integrity is a primary gate. Perturbation experiments separate mechanistic regimes, reduced ATP synthase capacity yields an “energized but unproductive” state with preserved Δψ but depressed ATP flux, whereas increased leak reduces usable output despite relatively preserved energization. Monte Carlo sensitivity analysis ranks Δψ and respiratory capacity as strongest correlates of ATP output, with ATP synthase capacity contributing positively and leak contributing negatively. A multi-state extension introduces explicit Δψ-ΔpH partitioning, finite CoQ redox pool dynamics , and cardiolipin-dependent supercomplex fraction S(t) , enabling diagnosis of organization kinetics and driving-force partition effects. Together, this syn-IMM platform provides an interpretable bridge between component-level reconstruction and system-level design, offering quantitative acceptance tests and design rules for programmable bioenergetic membranes.