Intracellular complement: Evidence, definitions, controversies, and solutions

Area of Science:

• Immunology
• Cell Biology

Background:

• The term "intracellular complement" is emerging to describe complement protein functions within cells.
• Current definitions are broad, leading to ambiguity in classification and localization.
• Understanding intracellular complement is crucial for deciphering its diverse biological roles.

Purpose of the Study:

• To review evidence for canonical and non-canonical functions of intracellular complement proteins.
• To discuss existing controversies and unanswered questions regarding intracellular complement.
• To propose refined terminology for accurate scientific discourse on intracellular complement.

Main Methods:

• Literature review of existing studies on intracellular complement.
• Analysis of evidence for complement protein localization and function within cellular compartments.
• Synthesis of current knowledge and identification of research gaps.

Main Results:

• Evidence supports both established (canonical) and novel (non-canonical) functions of complement proteins inside cells.
• Significant controversies and knowledge gaps persist regarding the precise nature and localization of intracellular complement.
• The current terminology is insufficient for precise scientific communication.

Conclusions:

• The concept of intracellular complement requires clearer definition and standardized terminology.
• Further research is needed to elucidate the mechanisms and specific roles of intracellular complement.
• Refined terminology will facilitate accurate discussion and advance understanding of intracellular complement activity.