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primary topic: Metformin induces iron deprivation and enhances mitochondrial ROS in macrophages creating a hostile environment for survival of intracellular Mycobacterium tuberculosis

Metformin induces iron deprivation and enhances mitochondrial ROS in macrophages creating a hostile environment for survival of intracellular Mycobacterium tuberculosis
type: AcademicArticle
type: Article
abstract: Diabetes, especially type 2 diabetic mellitus (T2DM) is associated with increased risk of contracting tuberculosis (TB). Though several factors, including immune system dysfunction, have been linked to this sensitivity the exact reasons have yet to be fully elucidated. Although metformin, a diabetic medication, has been suggested as a potential supplementary for host-directed therapy of tuberculosis, the mechanisms of its anti-TB effects remain unclear. Extremely virulent pathogens including M. tb require copious supplies of iron for their survival within host. Macrophages are a key player of innate immunity, and a target for invading mycobacteria to colonize. Upon infection macrophages attempt to withhold this strategic mineral from the pathogen and clear it. We sought to ascertain as to how anti-hyperglycemic medications like metformin affect the regulation of iron metabolism and oxidative stress. Our findings demonstrate that metformin decreases intracellular iron levels by decreasing the endocytosis of iron carrier protein transferrin. Studying macrophages in a cell culture model (in-vitro and ex-vivo) as well as from an in-vivo rodent model we observed that the recruitment of both classical and non-classical transferrin receptors (CD71 and GAPDH) to their surface was decreased. Metformin was also found to induce mitochondrial ROS production though cellular ROS was inhibited. Since iron and mitochondrial reactive oxygen species (mitoROS) are essential for regulating intra cellular Mycobacterium tuberculosis growth, our current findings indicate that metformin could be the first choice in the treatment for T2DM2 in individuals from tuberculosis-endemic areas and also as an adjunct therapeutic for TB patients in general.
date: 2025-08
volume: 189
issue: 118314
author list: authors
type: EPrint
type: ArticleEPrint
is part of: repository

Elsevier BV
type: Organization

Biomed. Pharmacother.
type: Collection

Chaaya Iyengar Raje
type: Person
given name: Chaaya Iyengar
family name: Raje

Manoj Raje
type: Person
given name: Manoj
family name: Raje

Anurag Sindhu
type: Person
given name: Anurag
family name: Sindhu

Sharmila Talukdar
type: Person
given name: Sharmila
family name: Talukdar

Radheshyam Modanwal
type: Person
given name: Radheshyam
family name: Modanwal

Rahul Dilawari
type: Person
given name: Rahul
family name: Dilawari

Gaurav Kumar Chaubey
type: Person
given name: Gaurav Kumar
family name: Chaubey

HTML Summary of #3245 Metformin induces iron deprivation and enhances mitochondrial ROS in macrophages creating a hostile environment for survival of intracellular Mycobacterium tuberculosis
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primary topic: Metformin induces iron deprivation and enhances mitochondrial ROS in macrophages creating a hostile environment for survival of intracellular Mycobacterium tuberculosis