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Updated: Jun 14, 2026
Alveolar Macrophage Phagocytosis and Bacteria Clearance in Mice
Published on: March 2, 2019
Zinc Promotes Mitochondrial Health Through PGC-1alpha Enhancing Bacterial Clearance in Macrophages Infected with
Ruxana T Sadikot1,2, Prabagaran Narayanasamy2, Zhihong Yuan2
1VA Nebraska Western Iowa Health Care System, Omaha, NE 68105, USA.
Abstract:
Mitochondria are increasingly recognized as important contributors to immune function, in addition to energy production. They exert this influence through modulation of various signaling pathways that regulate cellular metabolism and immune function in response to pathogens. Peroxisome proliferator-activated receptor (PPAR) coactivator 1 alpha (PGC-1α) is the primary transcription factor and regulator involved in mitochondrial biogenesis. Long known to be involved in immune function, zinc (Zn) is also required for proper mitochondrial function. It is increasingly recognized that many cellular immunometabolic activities are also Zn-dependent. Taken together, we investigated the role of Zn deficiency, both dietary and genetically induced, and Zn supplementation in PGC-1α-mediated macrophage mitochondrial biogenesis and immune function following infection with Mycobacterium avium complex (MAC). Our novel findings show that Zn is an important regulator of PGC-1α, TFAM and mitochondrial biogenesis, leading to enhanced bacterial phagocytosis and bacterial killing in macrophages. Mechanistically, we show that the Zn importer ZIP8 (Zrt/Irt-like protein) orchestrates Zn-mediated effects on PGC-1α and mitochondrial function. Taken together, defective Zn biodistribution may increase susceptibility to infection, whereas Zn supplementation may provide a tractable host-directed therapy to enhance the innate immune response in patients vulnerable to MAC infection.
Insights
Zinc is crucial for macrophage mitochondrial function and immune response. Zinc supplementation enhances bacterial phagocytosis and killing, offering a potential therapy for infections like Mycobacterium avium complex.
Area of Science:
- Immunometabolism
- Mitochondrial Biology
- Infectious Disease
Background:
- Mitochondria play key roles in immune function beyond energy production.
- Zinc (Zn) is essential for mitochondrial function and cellular immunometabolism.
- PGC-1α regulates mitochondrial biogenesis and is implicated in immune responses.
Purpose of the Study:
- To investigate the role of zinc deficiency and supplementation in PGC-1α-mediated macrophage mitochondrial biogenesis and immune function during Mycobacterium avium complex (MAC) infection.
- To elucidate the mechanism by which zinc influences PGC-1α and mitochondrial function.
Main Methods:
- Utilized dietary and genetically induced zinc deficiency models.
- Assessed macrophage mitochondrial biogenesis and immune function following MAC infection.
- Investigated the role of the zinc importer ZIP8.
Main Results:
- Zinc deficiency impairs PGC-1α, TFAM, and mitochondrial biogenesis.
- Zinc supplementation enhances macrophage phagocytosis and bacterial killing of MAC.
- The zinc importer ZIP8 mediates zinc's effects on PGC-1α and mitochondrial function.
Conclusions:
- Zinc is a critical regulator of PGC-1α and mitochondrial biogenesis in macrophages.
- Defective zinc biodistribution can increase infection susceptibility.
- Zinc supplementation represents a potential host-directed therapy to bolster innate immunity against MAC infection.
