Mitochondria, a semiautonomous, double-membrane organelle popularly known as the ‘powerhouses’ of the cells due to the fact that bulk source of energy in the form of ATP comes from mitochondria.

It is widely accepted from a very long time that oxidation of pyruvate, a glycolytic end product occurs in mitochondria, a phenomenon known as “aerobic respiration”.

As a result of pyruvate oxidation, reduced cofactors such a NADH generated which in turn drive the electron transport chain (ETC).

Complete oxidation generates about 36 moles of ATP from one mole of glucose typically require oxygen–respiring mitochondria. Although, this type of mitochondria exist from unicellular eukaryotes (protists) to mammals.

However, in many invertebrates such as Fasciola hepatica and mollusks, the mitochondria anaerobically respire and thus generate less amount of ATP as compare to typical aerobic respiration.

Mitochondria present in a group of unicellular eukaryotes popularly known as “hydrogenosomes” share some enzymatic similarity with typical mitochondrial enzymes involved in ATP homeostasis.

Human intestinal parasite Entamoeba histolytica possesses small, inconspicuous mitochondria known as Mitosomes, are not involved in ATP synthesis at all.

Existence of functional landscapes in mitochondria clearly indicates that mitochondrial origin follows phylogenetic evolution.

However, competing theories about mitochondrial evolution is still paradoxical. In 1970, Lynn Margulis proposed the idea that eukaryotic organelles such as mitochondria and chloroplasts evolved from free-living bacteria via symbiosis within a eukaryotic host cell that was later supported by others in the early 20th century.

Accumulating number of literature from the recent year supported the endosymbiont hypothesis of organelle origin using various molecular and cell biological experiments.

The earliest recognized hypothesis suggests that the divergence of alphaproteobacteria leads to mitochondrial evolution.

According to the endosymbiont hypothesis, once an independent prokaryote but later on mitochondria engulfed into host archaeon and retained as endosymbionts by then.

As a result of endosymbiosis, mitochondria participated in energy production, particularly ATP synthesis and also involved in reactive oxygen species detoxification for their host archaeon.

In another hypothesis proposed by Müller and Martin in 1998, popularly known as “hydrogen hypothesis” α-proteobacteria produce carbon source such as hydrogen (H2), carbon dioxide (CO2), and acetate and survival of archaeon was dependent on carbon source generated by α-proteobacteria.

High survival pressure on archaeon due to the limitation of carbon source leads to fusion of archaeon and α-proteobacteria.

As a consequence, α-proteobacteria utilize organic compounds provided by archaeon in order to generate H2, CO2, and acetate which support archaeon survival.

Nutritional-dependency turned-evolution of this metabolic symbiosis develop a mechanism of communication such acetate-mediated generation of acetyl-coA help to regulate enzymatic action via protein acetylation.

Moreover, acetylation of protein using acetate as a primary carbon source utilized by a variety of organism residing on the phylogenetic tree.

Moreover, superoxide generation by α-proteobacteria from respiratory chain also utilized as another medium of communication by oxidizing cysteine residue of proteins.

Over the course of evolution of this metabolic symbiosis, now mitochondria evolved and possess a very efficient machinery to generate energy as well as a variety of TCA metabolites that dictate cell fate.