• Ranjana

Arsenic is a globally pervasive environmental toxicant, with chronic exposure linked to multiorgan pathologies including hepatic, neurological, renal, cardiovascular, metabolic, and carcinogenic outcomes. Among the diverse molecular lesions induced by arsenic, disruption of proteostasis—encompassing protein misfolding, aggregation, endoplasmic reticulum (ER) stress, and mitochondrial dysfunction—represents a central axis of toxicity across organ systems. Arsenic’s strong thiophilic reactivity leads to covalent modification of protein cysteine residues, distortion of zinc-finger motifs, and disruption of metalloprotein active sites. These modifications trigger widespread misfolding, destabilization of protein tertiary structures, and overload of chaperone systems. Misfolded proteins accumulate in the ER lumen, activating the unfolded protein response (UPR) through the PERK, IRE1α, and ATF6 signaling pathways. Prolonged UPR signaling leads to inhibition of global translation, increased CHOP-mediated apoptosis, altered ER-associated degradation (ERAD), and dysregulated autophagy. Concurrently, arsenic impairs mitochondrial bioenergetics by inhibiting pyruvate dehydrogenase, α-ketoglutarate dehydrogenase, and electron transport chain complexes, producing excessive reactive oxygen species (ROS) and disrupting mitochondrial dynamics and membrane potential (ΔΨm). ER stress and mitochondrial dysfunction are mechanistically intertwined via mitochondria-associated ER membranes (MAMs), where Ca²⁺ flux and redox cycling generate feed-forward amplification loops that exacerbate proteotoxicity and oxidative injury. These molecular cascades converge to produce cytotoxicity, inflammation, fibrosis, and carcinogenesis. This chapter synthesizes high-resolution mechanistic insights into protein misfolding, ER stress, and mitochondrial dysfunction in arsenic toxicity, highlighting implications for biomarker development, therapeutic targeting, and public health—particularly in high-exposure regions such as Bihar, India.

Telomere Attrition, Genome Instability, Aging Biology, Cancer Initiation and Progression, Telomerase and ALT Pathways

"Telomere Attrition and Genome Instability: Shared Pathways in Aging and Cancer", International Journal of Emerging Technologies and Innovative Research (www.jetir.org), ISSN:2349-5162, Vol.13, Issue 1, page no.a33-a51, January-2026, Available :http://www.jetir.org/papers/JETIR2601005.pdf

"Telomere Attrition and Genome Instability: Shared Pathways in Aging and Cancer", International Journal of Emerging Technologies and Innovative Research (www.jetir.org | UGC and issn Approved), ISSN:2349-5162, Vol.13, Issue 1, page no. ppa33-a51, January-2026, Available at : http://www.jetir.org/papers/JETIR2601005.pdf