Mitochondrial Biology

apoptosis, calcium metabolism, cellular communication, and stress responses

• 13 essential protein subunits of the ETC • 22 tRNAs • 2 rRNAs

to estimate mitochondrial content or biogenesis/turnover (it can change depending on the number of mitochondria)

• mitochondria descend from a symbiotic relationship between an ancestral eukaryotic cell and a prokaryotic organism • this provided the host cell with the ability to perform oxidative phosphorylation i.e. more energy production • over time, most of the genes from the bacterial genome were transferred to the nuclear genome of the host cell through gene transfer and creating the mtDNA

• double membrane structure – suggests an engulfment process where the outer membrane originated from the host’s plasma membrane • own DNA and circular genome – similar to bacterial genomes; not enclosed in a nucleus and replicates independently through binary fission • bacterial-like ribosomes and protein synthesis – can synthesise some of their own proteins, independent of the nucleus • antibiotic sensitivity – certain antibiotics that inhibit bacterial ribosomes also affect mitochondrial protein synthesis i.e. bacterial origin

• mitochondrial dysfunction • release of cytochrome C • activation of cascade-9 at the apoptosome

Apaf-1 and cytochrome C

it inhibits the the release of cytochrome C from the mitochondrion and controls mitochondrial membrane permeability

activate downstream caspases caspase-3 and 7

they are constantly undergoing fission and fusion to maintain function

• fission - mediated by Drp1 and allows damaged mitochondria to be degraded by mitophagy and helps with cell division • fusion - mediated by Mitofusins and enables mitochondria to share contents, promoting metabolic efficiency and repair

• act as calcium buffers by sequestering excess cytosolic calcium, which could induce cell death • calcium storage within the mitochondrial matrix, often as insoluble calcium phosphate complexes • calcium uptake into mitochondria via the mitochondrial calcium uniporter activates enzymes in the TCA cycle

• excess calcium is released from the ER which leads to mitochondrial overload • overload triggers mitochondrial membrane to rupture, releasing caspase factors that promote apoptosis • cell dies due to programmed cell death mechanisms

• glycolysis • TCA cycle • ETC (inner mitochondrial membrane) • ATP synthesis (inner mitochondrial membrane)

to regenerate reduced coenzymes (NADH, FADH2) critical for the generation of more ATP via oxidative phosphorylation

3, 4, 6 and 8

1 ATP, 3 NADH, 1 FADH2 and 2 CO2

• Acetyl CoA • Citrate • Isocitrate • (alpha) Ketoglutarate • Succinyl CoA • Succinate • Fumarate • Malate • Oxaloacetate

• NADH and FADH2 generated from the TCA cycle release electrons and H+ • CoQ and cytochrome C carry electrons freed by the complexes • the 4 complexes generate a H+ gradient • ATP synthase uses the H+ gradient to convert ADP to ATP

complex II

to ensure proper ETC assembly and function, and to control mitochondrial stress adaptation

by producing ROS, which act as signalling molecules but can also cause damage if excessive

a selective form of autophagy that removes dysfunctional mitochondria to prevent cellular damage

by activating stress-response genes in the nucleus (acts in response to broader alterations and requires mito-nuclear communication)