BCL-2
The model captured the observation that BCL-2 overexpression suppresses basal and cisplatin-induced autophagy. Excess ER BCL-2 prevents autophagy initiation by binding Beclin-1, while excess mitochondrial BCL-2 prevents BH3 from crossing t…
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The model captured the observation that BCL-2 overexpression suppresses basal and cisplatin-induced autophagy. Excess ER BCL-2 prevents autophagy initiation by binding Beclin-1, while excess mitochondrial BCL-2 prevents BH3 from crossing the apoptotic threshold. Antiapoptotic BCL-2 family proteins at mitochondria oppose mitochondrial apoptosis, while BH3-only proteins promote it. BCL-2 overexpression was simulated by tripling ER and mitochondrial BCL-2. For population simulations, mitochondrial BCL-2 was sampled from a lognormal distribution to represent heterogeneous apoptotic thresholds.