Biostatistical Modeling of TI-A–CISD3 Fusion to Restore FAK Signaling and Mitochondrial Function in Age-Related Sarcopenia

Bilal Shafiq

doi:10.70749/ijbr.v3i11.2620

Authors

Bilal Shafiq M.Sc. Biotechnology, Coventry University, UK.

DOI:

https://doi.org/10.70749/ijbr.v3i11.2620

Keywords:

Sarcopenia, Focal Adhesion Kinase, TI-A–CISD3 Fusion, Mitochondrial Proteostasis, Protein-protein Interaction, in Silico Modeling, Pathway Analysis.

Abstract

Age-related sarcopenia, characterized by progressive loss of skeletal muscle mass and function, is driven by disrupted cellular signaling, oxidative stress, and mitochondrial dysfunction. Focal Adhesion Kinase (FAK, PTK2) serves as a central integrator of extracellular matrix (ECM)-mediated signals through integrin receptors, regulating cytoskeletal integrity, mechanotransduction, and anabolic pathways such as PI3K-Akt and MAPK. Dysregulation of FAK during aging impairs muscle anabolic signaling and proteostasis, contributing to functional decline. Using protein-protein interaction (PPI) network analysis and pathway mapping, FAK is identified as a highly connected hub interacting with structural and regulatory proteins, including EGFR, SRC, Talin, and Vinculin, highlighting its therapeutic potential. This study proposes a novel fusion protein combining plant-derived Trypsin Inhibitor A (TI-A) and the mitochondrial NEET protein CISD3 to simultaneously modulate FAK signaling at integrin-binding interfaces and enhance mitochondrial proteostasis. In silico methods including tertiary structure prediction, docking, molecular dynamics simulations, and network enrichment analysis demonstrate stable binding of TI-A to FAK and potential downstream regulation of autophagy, mitochondrial fission/fusion, and proteostasis markers (HSP70, PINK1, Parkin, DRP1). This integrative approach provides a mechanistic framework for predicting functional outcomes of dual-target interventions and underscores the utility of computational modeling and biostatistical analyses in therapeutic design. The TI-A–CISD3 fusion construct represents a multifunctional candidate capable of restoring anabolic signaling, improving mitochondrial homeostasis, and mitigating age-related sarcopenic decline.

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