Organelles are miscommunicating: Membrane contact sites getting hijacked by pathogens

ABSTRACT

Membrane Contact Sites (MCS) are areas of close apposition of organelles that serve as hotspots for crosstalk and direct transport of lipids, proteins and metabolites. Contact sites play an important role in Ca²⁺ signalling, phospholipid synthesis, and micro autophagy. Initially, altered regulation of vesicular trafficking was regarded as the key mechanism for intracellular pathogen survival. However, emerging studies indicate that pathogens hijack MCS elements – a novel strategy for survival and replication in an intracellular environment. Several pathogens exploit MCS to establish direct contact between organelles and replication inclusion bodies, which are essential for their survival within the cell. By establishing this direct control, pathogens gain access to cytosolic compounds necessary for replication, maintenance, escaping endocytic maturation and circumventing lysosome fusion. MCS components such as VAP A/B, OSBP, and STIM1 are targeted by pathogens through their effectors and secretion systems. In this review, we delve into the mechanisms which operate in the evasion of the host immune system when intracellular pathogens hostage MCS. We explore targeting MCS components as a novel therapeutic approach, modifying molecular pathways and signalling to address the disease’s mechanisms and offer more effective, tailored treatments for affected individuals.

KEYWORDS:

• Membrane contact sites (MCS)
• non-vesicular trafficking
• inter-organellar contacts
• host immune evasion
• direct lipid transport

Disclosure statement

No potential conflict of interest was reported by the author(s).

Author contributions

PP and BT wrote the manuscript. Both authors corrected and approved the final manuscript.

Data availability statement

No data sets were analysed in the manuscript and thus availability is not applicable.

Correction Statement

This article has been corrected with minor changes. These changes do not impact the academic content of the article.

Additional information

Funding

PP is supported by integrated MS-PhD fellowship from the Indian Institute of Science Education Research, Berhampur (IISER), Financial supports were from IISER Berhampur and Wellcome Trust DBT India to BT.