Fusion Peptide Separating ER and Mitochondria to Induce Autophagy
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Solution Overview
Problem
Current technologies lack an effective solution to inhibit the interaction between the endoplasmic reticulum and mitochondria, specifically the protein-protein interaction (PPI) between IP3R and GRP75 in MAMs, which is crucial for regulating autophagy and treating associated disorders.
Innovation Solution
A fusion peptide that inhibits the PPI between IP3R and GRP75 by increasing the distance between the endoplasmic reticulum and mitochondria, thereby regulating MAM activity and inducing autophagy.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Productivity
If the distance between endoplasmic reticulum and mitochondria is increased to inhibit their interaction, then intracellular autophagic activity is enhanced, but the efficiency of calcium transfer and energy metabolism regulation is reduced
Solution Approach 1:
The patent uses a fusion peptide consisting of a MAM-binding peptide and a mitochondria-targeting sequence as an intermediary molecule. This peptide specifically binds to MAM structures and induces their dissociation, thereby mediating the separation between endoplasmic reticulum and mitochondria. The intermediary peptide enables controlled disruption of organelle interactions to enhance autophagy while minimizing direct harmful effects on calcium transfer function.
Solution Approach 2:
The patent changes the spatial parameter (distance) between endoplasmic reticulum and mitochondria by introducing a fusion peptide that binds to MAM and induces structural rearrangement. This parameter change (increasing inter-organelle distance) directly promotes autophagic activity while the cell maintains calcium transfer efficiency through compensatory regulatory mechanisms.
2Use of energy by moving object
If MAM activity is inhibited to induce autophagy, then dysfunctional organelles are degraded for energy production, but cellular energy metabolism and lipid homeostasis regulation are impaired
Solution Approach 1:
The patent employs a dynamic approach by using a fusion peptide that can be introduced externally to temporarily disrupt MAM function only when autophagy induction is needed. The peptide binding to MAM is a reversible and controllable process, allowing the system to dynamically switch between normal MAM-mediated metabolism and autophagy-enhanced energy production based on cellular conditions.
Solution Approach 2:
The fusion peptide acts as a temporary intermediary that disrupts the normal MAM complex formation. By binding to MAM structures, the peptide prevents stable ER-mitochondria coupling, thereby inducing autophagy for energy production while the cell can restore normal metabolism once the peptide is removed or degraded.
3Productivity
If the interaction between IP3R and GRP75 is inhibited to increase autophagy, then intracellular organelle degradation is enhanced, but protein complex formation and signal transduction are disrupted
Solution Approach 1:
The fusion peptide serves as an intermediary that specifically targets and binds to the IP3R-GRP75 interaction interface or nearby MAM structures. By doing so, it disrupts the protein complex formation needed for normal signal transduction, thereby inducing autophagy. The peptide's temporary and reversible nature allows signal transduction to恢复正常 once the peptide is removed.
Solution Approach 2:
The patent extracts or removes the functional interaction between IP3R and GRP75 by introducing a fusion peptide that binds to one or both proteins, preventing their natural complex formation. This extraction of the specific protein-protein interaction enables autophagy induction while the cell can restore normal signaling through alternative pathways or upon peptide removal.
Data Source
AI summary
The present disclosure relates to a peptide for inhibiting PPI between IP3R and GRP75 in MAM, and a composition for preventing, alleviating or treating a disease related to autophagy disorder containing the same as an active ingredient.The features and advantages of the present disclosure may be summarized as follows:(a) The present disclosure provides a peptide capable of inducing intracellular autophagy by inhibiting the interaction between the endoplasmic reticulum and mitochondria, more specifically the PPI between IP3R and GRP75 in MAM, by regulating the activity of MAM.(b) The peptide of the present disclosure can be usefully applied to alleviate or treat a disease related to autophagy disorder, especially a disease caused by abnormal protein accumulation induced by reduced intracellular autophagy or a degenerative disease.