Zinc cytotoxicity induces mitochondrial morphology changes in hela cell line.

Abstract

Zinc (Zn²⁺) is important in cellular processes. In the cell, free zinc is tightly regulated and found in minuscule amounts. However, in an unhealthy cellular environment, such as hypoxia, zinc increases in the cell and zinc overload may occur. Studies have shown that zinc overload causes cellular and mitochondrial stress. Mitochondrial stress affects mitochondrial morphology. In normal cells, mitochondrial morphology resembles a long, tubular shape. In unhealthy cells, mitochondrial morphology resembles fragmented, circular shape. To address whether zinc overload contributes directly to the abnormal changes of mitochondrial morphology, we imaged and analyzed mitochondria that were treated with the application of exogenous zinc. In the first part of the study, exogenous zinc was applied to HeLa cells at 1 µM, 10 µM, 50 µM, 100 µM, or 200 µM zinc chloride along with 10 µM pyrithione. Mitochondrial morphology was analyzed with Mito-Morphology micro in ImageJ. Mitochondrial morphology changed from a healthy tubular shape to an unhealthy circular shape and fragmentation. Mitochondrial morphology changes were observed in a dose-dependent fashion. The second part of the study involved applying the metal ion chelator TPEN after applying 50 µM zinc chloride along with 10 µM pyrithione. TPEN reduced zinc-induced abnormal mitochondrial morphology after zinc treatment. This present study supports that zinc overload may cause morphology changes induced by mitochondrial stress that may lead to cell death.