Mitochondria as intracellular signaling platforms in health and disease

Abstract

Mitochondria, long viewed solely in the context of bioenergetics, are increasingly emerging as critical hubs for intracellular signaling. Due to their bacterial origin, mitochondria possess their own genome and carry unique lipid components that endow these organelles with specialized properties to help orchestrate multiple signaling cascades. Mitochondrial signaling modulates diverse pathways ranging from metabolism to redox homeostasis to cell fate determination. Here, we review recent progress in our understanding of how mitochondria serve as intracellular signaling platforms with a particular emphasis on lipid-mediated signaling, innate immune activation, and retrograde signaling. We further discuss how these signaling properties might potentially be exploited to develop new therapeutic strategies for a range of age-related conditions.

Mitochondrial Functionality in Inflammatory Pathology-Modulatory Role of Physical Activity

“…A growing body of evidence highlights the key role of mitochondria, in addition to the ROS-mediated mechanisms, in innate immunity. The reader is referred to some excellent new reviews on the topic [ 65 , 66 ], because we will not describe in detail these molecular mechanisms. In brief, when viruses reach the cytoplasm, RNAs perceived as foreign activate the aggregation of an outer mitochondrial membrane protein called mitochondrial antiviral-signaling protein (MAVs).…”

“…In brief, when viruses reach the cytoplasm, RNAs perceived as foreign activate the aggregation of an outer mitochondrial membrane protein called mitochondrial antiviral-signaling protein (MAVs). MAV aggregation induces the expression factor kappa light chain enhancer of activated B cell (NF-kB) and type I interferons via interferon regulatory factors (IRFs) in the nucleus, thereby leading to antiviral defense [ 65 , 66 ].…”

“…It has been reported that mitochondrial dynamics (i.e., balance between mitochondrial fusion and fission) and mitophagy seem to be important to the regulation of immune response to virus infection [ 67 ]. In fact, some viruses are able to alter the innate immune system in cells by increasing DRP1 s616 phosphorylation [ 68 ], which ultimately results in mitochondrial fragmentation and dysfunction [ 66 ]. Additionally, peripheral mononuclear cells showed altered mitochondrial metabolism by SARS-CoV-2 in patients with COVID-19 [ 69 ].…”

Mitochondrial-Encoded Peptide MOTS-c is an Exercise-Induced Regulator of Aging Metabolic Homeostasis and Physical Capacity

“…MOTS-c acts as an intracellular and endocrine factor, thus has been dubbed a mitochondrial-encoded hormone or a mitochondrial cytokine (mitokine) 2,10,16,49,57-59 . Understanding the detailed molecular details of MOTS-c function as an endocrine factor is an ongoing investigation at multiple ends, including its cellular uptake.…”

“…Mitochondria are strongly implicated in aging at multiple levels 1,2,24,63-65 and MOTS-c may contribute to longevity by promoting cellular homeostasis 2,10,57-59 . Here, we present evidence that the mitochondrial genome encodes for instructions to maintain physical capacity ( i.e.…”