Microscopic view of a cancer cell undergoing mitophagy

Cellular Housekeeping: How Mitophagy Impacts Cancer Treatment

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Lena Kashyap in Health & Wellness December 2025 • 4 min read.

"Unlocking the Secrets of How Cells Clean Themselves to Improve Cancer Therapies"


In the ongoing battle against cancer, scientists are constantly seeking new ways to improve treatments and outcomes. One promising area of research focuses on oncolytic viruses, which are designed to selectively target and destroy cancer cells while leaving healthy cells unharmed. Newcastle disease virus (NDV) is one such virus that has shown potential in clinical studies, but understanding exactly how it works is crucial for maximizing its effectiveness.

Apoptosis, or programmed cell death, is a key mechanism by which NDV exerts its anti-tumor effects. However, cancer cells are crafty and can develop ways to resist apoptosis, hindering the virus's ability to eliminate them. Autophagy, a cellular process that involves the breakdown and recycling of damaged or unnecessary components, can further complicate matters. While autophagy can protect cells under stress, including during viral infection, its role in the context of NDV therapy has remained unclear.

Recent research has shed light on the intricate interplay between NDV, apoptosis, and a specific type of autophagy called mitophagy. Mitophagy is the selective removal of damaged mitochondria, the powerhouses of the cell. Scientists are now discovering that NDV can manipulate mitophagy to its advantage, promoting its own replication and potentially reducing the effectiveness of cancer treatments. This article delves into these findings, exploring how understanding and targeting mitophagy could revolutionize cancer therapy.

Mitophagy: The Key to Viral Replication?

Microscopic view of a cancer cell undergoing mitophagy

A new study reveals that NDV, particularly the La Sota strain, triggers autophagy in non-small cell lung cancer cells. This induced autophagy helps the virus to replicate more effectively by preventing cancer cells from undergoing caspase-dependent apoptosis, a critical process of programmed cell death. Researchers found that when autophagy was active, cancer cells were less likely to self-destruct, allowing the virus to thrive and multiply.

Further investigation showed that NDV recruits a specific protein, SQSTM1, to initiate mitophagy. This process controls the release of cytochrome c, a molecule that triggers intrinsic pro-apoptotic signaling. By preventing the release of cytochrome c, NDV effectively blocks the internal signals that would otherwise lead to cell death. It’s like the virus is cleaning house, removing anything that could trigger the cell’s self-destruct mechanism.

  • SQSTM1 Recruitment: NDV utilizes SQSTM1 to target and remove damaged mitochondria.
  • Cytochrome c Control: Mitophagy prevents the release of cytochrome c, blocking apoptosis.
  • Enhanced Viral Replication: By inhibiting apoptosis, NDV promotes its own replication within cancer cells.
To test this theory, researchers used 3-methyladenine (3-MA), an autophagy inhibitor, in conjunction with NDV. They observed that when autophagy was blocked, the oncolytic effect of NDV was enhanced, meaning that more cancer cells were killed. Interestingly, the timing of the 3-MA administration was crucial. Postponing the administration of 3-MA to 24 hours after NDV infection resulted in a more profound anti-tumor effect. This suggests that allowing the virus to initially replicate before blocking autophagy can maximize the therapeutic outcome.

A New Therapeutic Avenue?

These findings unveil a novel strategy by which NDV manipulates mitophagy to promote its replication by blocking apoptosis. This provides a rationale for combining NDV with autophagy inhibitors in cancer therapy. By strategically timing the administration of autophagy inhibitors, it may be possible to enhance the oncolytic effects of NDV and improve patient outcomes. This approach requires further investigation and could represent a significant advancement in NDV-based virotherapy.

About this Article -

This article was crafted using a human-AI hybrid and collaborative approach. AI assisted our team with initial drafting, research insights, identifying key questions, and image generation. Our human editors guided topic selection, defined the angle, structured the content, ensured factual accuracy and relevance, refined the tone, and conducted thorough editing to deliver helpful, high-quality information.See our About page for more information.

Everything You Need To Know

1

What exactly is mitophagy, and why should I care about it?

Mitophagy is a specific type of autophagy. It is the selective removal of damaged mitochondria, which are the powerhouses of the cell. This process is crucial for maintaining cellular health by eliminating dysfunctional mitochondria that could otherwise harm the cell. In the context of cancer and viral infections, like those involving Newcastle disease virus (NDV), mitophagy can play a significant role by influencing cell survival and death pathways.

2

What is Newcastle disease virus (NDV) and why is it important in cancer treatment?

Newcastle disease virus (NDV) is significant because it's an oncolytic virus, meaning it can selectively target and destroy cancer cells while ideally leaving healthy cells unharmed. The La Sota strain of NDV can induce autophagy to help the virus replicate more effectively by preventing cancer cells from undergoing caspase-dependent apoptosis.

3

Can you explain apoptosis and its role in cancer treatment?

Apoptosis, or programmed cell death, is a critical mechanism by which treatments like oncolytic viruses such as Newcastle disease virus (NDV) exert their anti-tumor effects. It's the process where cells self-destruct in a controlled manner, preventing damage to surrounding tissues. However, cancer cells often develop resistance to apoptosis, which can hinder the effectiveness of cancer therapies. Overcoming this resistance is a key focus in cancer research and treatment strategies.

4

What is SQSTM1, and how does it relate to mitophagy and viral infections?

SQSTM1 is a protein that NDV recruits to initiate mitophagy. By using SQSTM1, the virus targets and removes damaged mitochondria, preventing the release of cytochrome c, a molecule that triggers apoptosis. Therefore, SQSTM1 is a key player in NDV's strategy to block the cell's self-destruct mechanism and promote viral replication. The use of SQSTM1 is vital to enhanced viral replication.

5

What is 3-methyladenine (3-MA), and how does it impact cancer treatment in conjunction with NDV?

3-methyladenine (3-MA) is an autophagy inhibitor. When used in conjunction with Newcastle disease virus (NDV), 3-MA can enhance the oncolytic effect of the virus, leading to increased cancer cell death. Timing is crucial. Postponing the administration of 3-MA to 24 hours after NDV infection results in a more profound anti-tumor effect, suggesting that allowing the virus to initially replicate before blocking autophagy maximizes the therapeutic outcome.

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